Terhune v. Secretary of Health and Human Services

In the United States Court of Federal Claims
OFFICE OF SPECIAL MASTERS
No. 16-393V
Originally Filed: December 17, 2021
Filed in Redacted Form: January 13, 2022
PUBLISHED

Special Master Horner
A.T.,

Petitioner, Ruling on the Written Record;
v. Narcolepsy Cataplexy
Syndrome; Human
SECRETARY OF HEALTH AND Papillomavirus (“HPV”) vaccine
HUMAN SERVICES,

Respondent.

Danielle Strait, Maglio Christopher & Toale, P.A., Seattle, WA, for petitioner.
Catherine Stolar, U.S. Department of Justice, Washington, DC, for respondent.

DECISION 1

On March 29, 2016, petitioner, A.T. 2, filed a petition under the National Childhood
Vaccine Injury Act, 42 U.S.C. § 300aa-10-34 (2012), 3 alleging that her receipt of a
second human papillomavirus (“HPV”) vaccine on May 1, 2013 caused-in-fact, or
alternatively, significantly aggravated her narcolepsy with cataplexy. 4 (ECF No. 1.) For
the reasons set forth below, I conclude that petitioner is not entitled to an award of
compensation.

1 When this decision was originally filed the undersigned advised his intent to post it on the United States
Court of Federal Claims' website, in accordance with the E-Government Act of 2002. 44 U.S.C. § 3501
note (2012) (Federal Management and Promotion of Electronic Government Services). In accordance
with Vaccine Rule 18(b), petitioner filed a timely motion to redact certain information. This decision is
being reissued with petitioner’s name reduced to initials. Except for those changes and this footnote, no
other substantive changes have been made. This decision will be posted on the court’s website with no
further opportunity to move for redaction.

2 Petitioner was a minor when the petition was filed, so her mother filed the petition as her legal
representative. Petitioner reached the age of majority on March 27, 2017 and was substituted as
petitioner on December 19, 2017. (ECF Nos. 30, 31.)

3 All references to “§ 300aa” below refer to the relevant section of the Vaccine Act at 42 U.S.C. § 300aa-

10-34.

4 The brand name of the HPV vaccine administered to petitioner is Gardasil. (See Ex. 21.)

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 I. Applicable Statutory Scheme

Under the National Vaccine Injury Compensation Program, compensation
awards are made to individuals who have suffered injuries after receiving vaccines. In
general, to gain an award, a petitioner must make a number of factual demonstrations,
including showing that an individual received a vaccination covered by the statute;
received it in the United States; suffered a serious, long-standing injury; and has
received no previous award or settlement on account of the injury. Finally – and the key
question in most cases under the Program – the petitioner must also establish a causal
link between the vaccination and the injury. In some cases, the petitioner may simply
demonstrate the occurrence of what has been called a “Table Injury.” That is,
petitioners may show that they suffered an injury of the type enumerated in the “Vaccine
Injury Table,” corresponding to the vaccination in question, within an applicable time
period following the vaccination also specified in the Table. In such cases, the Table
Injury is presumed to have been caused by the vaccine. § 300aa-13(a)(1)(A); § 300 aa-
11(c)(1)(C)(i); § 300aa-14(a); § 300aa-13(a)(1)(B).

In many cases, however, the vaccine recipient may have suffered an injury not
covered by the Vaccine Injury Table. In these “off-Table” cases, an alternative means
exists to demonstrate entitlement to a Program award. The petitioner may demonstrate
entitlement by showing that the recipient’s injury was “caused-in-fact” by the vaccine
they received, a showing often referred to as “actual causation.” § 300aa-13(a)(1)(B); §
300aa-11(c)(1)(C)(ii). In off-table cases, the presumptions available under the Vaccine
Injury Table are inoperative, and the burden is on the petitioner to introduce evidence
demonstrating that the vaccination was responsible for the injury in question. Althen v.
Sec’y of Health & Human Servs., 418 F.3d 1274, 1278 (Fed. Cir. 2005); Hines v. Sec’y
of Health & Human Servs., 940 F.2d 1518, 1525 (Fed. Cir. 1991).

To show actual causation, petitioner must satisfy the “preponderance of the
evidence” standard, the same standard ordinarily used in tort litigation. § 300aa-
13(a)(1)(A); see also Althen, 418 F.3d at 1279; Hines, 940 F.2d at 1525. Under that
standard, the petitioner must show that it is “more probable than not” that the
vaccination caused the alleged injury. Althen, 418 F.3d at 1279. The petitioner need
not show that the vaccination was the sole cause of the injury or condition, but must
demonstrate that the vaccination was a “substantial factor” and a “but for” cause.
Shyface v. Sec’y of Health & Human Servs., 165 F.3d 1344, 1352 (Fed. Cir. 1999).
This standard has been interpreted to require “proof of a logical sequence of cause and
effect showing that the vaccination was the reason for the injury;” the logical sequence
must be supported by “reputable medical or scientific explanation, i.e., evidence in the
form of scientific studies or expert medical testimony.” Althen, 418 F.3d at 1278; Grant
v. Sec’y of Health & Human Servs., 956 F.2d 1144, 1148 (Fed. Cir. 1992). A petitioner
may not receive a Vaccine Program award based solely on his or her assertions; rather,
the petition must be supported by either medical records or by the opinion of a
competent physician. § 300aa-13(a)(1).

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 In what has become the predominant framing of this burden of proof, the Althen
court described the “causation-in-fact” standard, as follows:

Concisely stated, Althen’s burden is to show by preponderant evidence
that the vaccination brought about her injury by providing: (1) a medical
theory causally connecting the vaccination and the injury; (2) a logical
sequence of cause and effect showing that the vaccination was the reason
for the injury; and (3) a showing of proximate temporal relationship
between vaccination and injury. If Althen satisfies this burden, she is
“entitled to recover unless the [government] shows, also by a
preponderance of the evidence, that the injury was in fact caused by
factors unrelated to the vaccine.”

Althen, 418 F.3d at 1278 (citations omitted). The Althen court noted that a petitioner
need not necessarily supply evidence from medical literature supporting petitioner’s
causation contention, so long as the petitioner supplies the medical opinion of an
expert. Id. at 1279-80. That expert’s opinion must be “sound and reliable.” Boatmon v.
Sec’y of Health & Human Servs., 941 F.3d 1351, 1359-60 (Fed. Cir. 2019). The Althen
court also indicated, however, that a Program fact finder may rely upon “circumstantial
evidence,” which the court found to be consistent with the “system created by Congress,
in which close calls regarding causation are resolved in favor of injured claimants.”
Althen, 418 F.3d at 1280.

Where a petitioner in an off-Table case is seeking to prove that a vaccination
aggravated a pre-existing injury, petitioners must also establish three additional factors.
See Loving v. Sec’y of Health & Human Servs., 86 Fed. Cl. 135, 144 (Fed. Cl. 2009)
(combining the first three Whitecotton factors for claims regarding aggravation of a
Table injury with the three Althen factors for off table injury claims to create a six-part
test for off-Table aggravation claims); see also W.C. v. Sec’y of Health & Human Servs.,
704 F.3d 1352, 1357 (Fed. Cir. 2013) (applying the six-part Loving test.). The additional
Loving factors require petitioners to demonstrate aggravation by showing: (1) the
vaccinee’s condition prior to the administration of the vaccine, (2) the vaccinee’s current
condition, and (3) whether the vaccinee’s current condition constitutes a “significant
aggravation” of the condition prior to the vaccination. Id.
In this case, petitioner filed her petition alleging that her receipt of a second HPV
vaccine caused, or alternatively, significantly aggravated her narcolepsy. (ECF No. 1.)
However, petitioner now contends only that the HPV vaccine significantly aggravated
her narcolepsy. (See ECF Nos. 26-28, 73.) Because this injury is not listed as a Table
Injury relative to the HPV vaccine, petitioner must satisfy the six-part Loving test. See
42 C.F.R. § 100.3(a).

II. Procedural History

Petitioner’s mother filed a petition on her behalf on March 29, 2016. (ECF No.1.)
Petitioner was later substituted as petitioner once she reached the age of majority.
(ECF Nos. 30, 31.) The case was assigned to Special Master Laura Millman. (ECF No.

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4.) Petitioner filed supporting medical records marked as Exhibits 1-7 on April 7, 2016.
(ECF No. 6.) Following an initial status conference on May 19, 2016, petitioner
submitted additional medical records, petitioner’s mother’s affidavit, and a Statement of
Completion. (Exs. 8-12, ECF Nos. 9, 11, 12.)

On May 19, 2016 Special Master Millman issued an order, noting that statements
made by petitioner’s mother in her medical records regarding symptom onset “[we]re
not consistent.” (ECF No. 8.) Special Master Millman observed that petitioner’s mother
reported on May 11, 2013 “that [petitioner’s] narcolepsy worsened two weeks before
[petitioner] received the Gardasil vaccine,” but claimed “just three days later on May 14,
2013,” that petitioner’s “symptoms increased after she received the vaccination.” (ECF
No. 8 (citing Ex. 4, pp. 52, 63).)

On August 23, 2016 Special Master Millman issued a subsequent order, and
again noted that “[petitioner’s] medical records show that she was experiencing
symptoms of narcolepsy cataplexy syndrome before she received her second Gardasil
vaccine on May 1, 2013.” (ECF No.13, citing Ex. 4, p. 52; Ex. 11, pp. 2, 31.) Special
Master Millman ordered petitioner’s mother to file an affidavit explaining the discrepancy
in the records regarding the alleged onset of her daughter’s injury. (Id.) Petitioner’s
mother filed an affidavit on September 22, 2016 wherein she alleged that “[t]here was
nothing wrong with my daughter on May 1, 2013. She was given two vaccines that day,
hepatitis and the second Gardasil.” (ECF No. 14, Ex. 13, p. 1.)

Following a telephonic status conference, on September 26, 2016 Special Master
Millman noted that she felt this was a significant aggravation case and ordered
petitioner to file an expert report supporting her claim. (ECF. No. 15.) On November
27, 2017, Special Master Millman issued an order questioning whether it was
reasonable to proceed. (ECF No. 26.) Concurrently, Special Master Millman filed Court
Exhibit 1, an epidemiological study “showing that among almost one million adolescent
girls, [the] HPV vaccine was not [r]elated causally to narcolepsy.” (ECF No. 26.)5 On
December 11, 2017, Special Master Millman granted petitioner’s Motion for Clarification,
finding this case to be an allegation that petitioner’s second HPV vaccine significantly
aggravated her preexisting narcolepsy-cataplexy. (ECF Nos. 27, 28.)

On February 8, 2018, petitioner filed her first expert report from Dr. Lawrence
Steinman and additional medical literature. (ECF Nos. 39-41, Exs. 14-39.) On May 18,
2018, respondent filed his Rule 4(c) report, arguing that the evidence presented did not
meet petitioner’s burden and recommending against compensation. (ECF No. 46.)
Respondent also filed medical literature and expert reports from Dr. Maryann Deak
(neurology and sleep medicine) (Ex. A) and Dr. Lindsay Whitton (virology and
immunology) on the same day. (Ex. C) (ECF No. 43.) Each party subsequently filed

5 Special Master Millman also noted the increased incidence of narcolepsy following the Pandemrix (2009
H1N1 flu vaccine) and the H1N1 flu virus “suggests that that the flu virus in the 2009 H1N1 flu vaccine,
not the adjuvant, was responsible for the increase in narcolepsy cases. HPV does not contain H1N1 flu
virus.” (ECF No. 26, p. 2.)

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additional expert reports and the case was later reassigned to me on June 5, 2019.
(Exs. 40, 43, 49, 55; Exs. EE, GG, KK, RR; ECF No. 57 (Notice of Reassignment).)

On August 25, 2020 I held a status conference to discuss possible resolution of
petitioner’s claim, proposing a resolution based on the written record. (ECF No. 71.)
The parties agreed. 6 (Id.) Petitioner filed her Motion for a Ruling on the Record on
December 18, 2020. (ECF No. 73.) Respondent filed her response to petitioner’s
motion on March 22, 2021 and petitioner filed her reply to respondent’s response to
petitioner’s motion on April 13, 2021. (ECF Nos. 75, 76.)

I have determined that the parties have had a full and fair opportunity to present
their cases and that it is appropriate to resolve this issue without a hearing. See Vaccine
Rule 8(d); Vaccine Rule 3(b)(2); Kreizenbeck v. Sec’y of Health & Human Servs., 945
F.3d 1362, 1366 (Fed. Cir. 2020) (noting that “special masters must determine that the
record is comprehensive and fully developed before ruling on the record.”).
Accordingly, this matter is now ripe for resolution.

III. Medical History

Petitioner was born on March 27, 1999. (Ex. 2, p. 3.) Prior to vaccination,
petitioner suffered only minor health issues, including a history of congenital cataract at
age two and obstructive sleep apnea requiring a tonsillectomy at age five. (Ex. 3, p.
55.) On April 2, 2012, petitioner received her first HPV vaccination at 13 years of age.
(Ex. 4, p. 74.) Then on May 1, 2013, petitioner presented to her pediatrician, Sidney
Randel, M.D., for her routine well visit. (Ex. 4, p. 70.) Dr. Randel’s physical
examination of petitioner was normal. 7 (Id. at 71.) Dr. Randel noted “[f]ine and gross
motor sensory intact,” petitioner’s deep tendon reflexes were equal, no pathological
reflex; petitioner’s tone was normal, no focal deficits; and petitioner’s gait was normal
and appropriate for her age. (Id.) He recorded that petitioner was overweight but a
“well child.” 8 (Id. at 72.) Dr. Randel discussed with petitioner a healthy diet and
6 I also advised the parties that “[i]f upon preparing their written submissions either party comes to
believe that this case is not ripe for resolution on the existing record, they may address those concerns in
the form of a motion to amend the schedule. Otherwise, the parties should anticipate that I will resolve the
question of petitioner’s entitlement to compensation without further proceedings.” (ECF No. 71.) No such
motion was filed.

7 The record notes in the section “Patient/Parent Questions,” that “Mom says [petitioner] does not sleep.”

(Ex. 4, p. 70.)
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Later accounts of petitioner’s symptoms reveal a history of sleep disruption and daytime sleepiness with
prolonged napping prior to her hospitalization on May 11, 2013 for four to six weeks, discussed further
below. (Ex. 3, p. 43, Ex. 4, p. 52 (Dr. Neidenberg); Ex. 3, p. 84-85 (Dr. Martinez); Ex. 3, pp. 5-6, Ex. 4,
pp. 9-10, Ex. 11, pp. 31-33 (Dr. Dubrovsky); Ex. 3, pp. 64-67 (Dr. Brown); Ex. 3, pp. 48-50 (Dr. Maragh),
Ex. 3, pp.54-55 (Dr. Chiang); Ex. 3, pp. 67-68 (Dr. Gutierrez).) In one note, petitioner described “waking
up 1-2 [times] a night 4 weeks ago.” (Ex. 3, p. 5.) This would place onset of petitioner’s symptoms in
approximately April 2013. Between 2-4 weeks prior to hospitalization, petitioner reported additional
symptoms including: legs buckling (Ex. 3, p. 65, Ex. 3, p. 85), falls (Ex. 3, p. 65, Ex. 3, p. 69), slurred
speech (Ex. 3, pp. 5-6), and gait difficulties (Ex. 3, p. 69, Ex. 3, p. 85). Petitioner does not allege that her
narcolepsy began after the May 1, 2013 vaccination. (ECF No. 73, p. 14.)

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exercise. (Id.) Petitioner also received a Hepatitis A vaccination and her second HPV
vaccination. (Id. at 71.)

On May 11, 2013, ten days after receiving her second HPV vaccination,
petitioner presented to the emergency department at Joe DiMaggio Children’s Hospital
complaining of sleeplessness, weakness, twitching and slurred speech. (Ex. 3, p. 43.)
Petitioner’s mother reported a history of petitioner’s symptoms to Ilhana Gilderman
Neidenberg, D.O. (Id.) The history of present illness included: a six-week history of
“sleeplessness,” a two-and-a-half-week history of “knees twitching while standing,” and
a three-day history of “slurred speech and hands twitching and shaking.” (Id.)
Petitioner’s mother also remarked that “sometimes [petitioner] can[not] stand up without
leaning against the wall because she is disoriented.” (Id.) According to petitioner’s
mother, she had “fallen down several times” because petitioner was unaware of her fall
or unable to catch herself. (Id.) Petitioner’s history of present illness also noted that
she was able to fall asleep at night, only to “wake up a few hours later unable to fall
asleep.” (Id.)

Petitioner’s mother further reported to Dr. Neidenberg that she attributed
petitioner’s sleeplessness to the end of the soccer season, approximately six weeks
prior, concluding that she “was not getting enough exercise to tire her out.” (Ex. 3, p.
43.) The history of present illness also documented a six-week history of prolonged
naps after school lasting three hours. (Id.) Petitioner’s mother reported that her
symptoms “have worsened so she brought [petitioner] to [primary care provider] 2
weeks ago where she received Gardasil vaccine and [the pediatrician] also
recommended melatonin for sleeplessness with no relief.” (Id.) Petitioner was admitted
to the hospital May 11, 2013 for further evaluation. (Id. at 46.)

Later that day, petitioner was seen by Diana Martinez, M.D., for a neurology
consult. (Ex. 3, p. 47) CT and EEG results were reviewed as normal. (Id. at 56.) The
MRI was reported as normal and the MRA of the brain was inconclusive due to
interference from petitioner’s braces. (Id. at 58.) Dr. Martinez recommended a thyroid
function test and that infectious disease be contacted to see whether “this could
possibly be a side effect of [G]ardasil, although [she had] never seen this.” (Id. at 90.)
In her neurological exam Dr. Martinez observed that “when [petitioner] got up to use the
bathroom she felt loss of balance and had some twitches….” (Id. at 92.)

On May 12, 2013 Dr. Martinez returned for a follow-up and noted in the
subjective portion of the medical record that petitioner’s “[m]other has concerns that the
[petitioner] had a [G]ardasil immunization a[nd] this may have contributed to the
[petitioner’s] symptoms.” (Id. at 99-100.) Dr. Martinez’s assessment noted that “the
etiology of [petitioner’s] symptoms [is] unknown[;] it’s possible that this is related to the
green coffee extract [petitioner] was taking.” (Id. at 102.)

On May 13, 2013, pediatric neurologist Tatyana Dubrovsky, M.D., met with
petitioner and noted that petitioner had received a “Gardasil vaccination 2 weeks ago.”
(Ex. 3, p. 5.) Dr. Dubrovsky questioned whether “the vaccination has anything to do

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with the escalat[ion] of the symptoms” petitioner was experiencing. (Id. at 6.) In the
physical exam, Dr. Drubrovsky noted that petitioner “actually had an episode” where
she began slurring her speech and nodding her head. (Id.) The same day, pediatric
infectious disease specialist Robert Reid, M.D., examined petitioner for “suspected
toxicity from Gardasil vaccine.” (Id. at 51.) Dr. Reid concluded that petitioner’s
condition was “not likely a reaction to the vaccine since the symptoms of insomnia
started way before the vaccine was given.” (Id. at 53.)

On May 14, 2013, petitioner was seen by pediatric neurologist Stuart Brown,
M.D. (Ex. 3, pp. 65-66.) Dr. Brown noted that petitioner received a Gardasil vaccination
approximately two weeks prior and “[s]ince that time, her symptoms have seemingly
increased, but she has also been noticing, and the mother has been noticing, that in the
last week she has not only been falling, but she has been having difficulty in walking,
being very unsteady on her feet.” (Id. at 65.) Dr. Brown also questioned whether
petitioner’s Gardasil vaccination “triggered [] narcolepsy on an autoimmune basis,” and
observing that “[t]his has been reported occasionally with other immunizations.” (Id. at
66.) Dr. Brown further commented that “[a]lthough Gardasil was thought to perhaps be
associated with increased precipitation of Guillain-Barre Syndrome, the statistics for this
are questionable as to a cause and effect relationship.” (Id.)

On May 15, 2013, petitioner was seen by pediatric infectious disease specialist
Maria Gutierrez, M.D. (Ex. 3, p. 68.) In her consultation, Dr. Gutierrez noted that
“[s]ome sleep disturbance, narcolepsy, have been associated with previous infections.
There have also been cases of narcolepsy associated with Influenzae [sic] vaccine with
an adjuvant that is not available in this country.” (Id. at 70.) Dr. Gutierrez also observed
that petitioner “had received the Gardasil [vaccination] after the symptoms had started”
and “d[id] not believe there has been association.” (Id.) On May 16, 2013 petitioner
had a consultation with pediatric allergist and immunologist Gary Kleiner, M.D. (Ex. 3,
p. 62.) Dr. Kleiner noted that petitioner’s “mother believes that some of [petitioner’s]
symptoms may have occurred shortly after her Gardasil vaccination.” (Id. at 62-63.) Dr.
Kleiner requested a follow-up visit to review petitioner’s pending lab results. (Id. at 63-
64.) Petitioner’s lab results ultimately revealed that she had the HLA DQB1*0602 gene
and low hypocretin, consistent with narcolepsy. 9 (Ex. 2, p. 4; Ex. 11, p.103.)

Petitioner was discharged from the hospital on May 17, 2013 after receiving
intravenous immunoglobulin for treatment of possible autoimmune narcolepsy. (Ex. 3,
p. 72; Ex. 11, p. 2.) The discharge summary, dated May 16, 2013, indicates that
petitioner was seen by two infectious disease physicians, Drs. Reid and Gutierrez, and
three neurologists, Drs. Martinez, Dubrovsky and Brown and that her “presumptive
diagnosis [wa]s narcolepsy.” (Ex. 11, p. 3.) Her symptoms were listed as “ongoing but
not worsening.” (Id.) On May 23, 2013 petitioner returned to see Dr. Dubrovsky for a
follow-up appointment. (Ex. 11, p. 31.) The history of present illness noted that

9 It is not clear from the records when these lab results were reported, but petitioner appears to have

been discharged prior to the tests’ completion. (Ex. 11, pp. 3-7) (lab results available at discharge do not
include hypocretin or genetic testing results) (But see Ex. 2, p. 4; Ex. 11, p. 103) (reporting test results
from May 14, 2013).)

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petitioner “presented with excessive daytime sleepiness, cataplexy, and episodes of
sleep paralysis since mid-April, exacerbated after Gardasil shot at the end of April.”
(Id.) Per her assessment, Dr. Dubrovsky noted that she was “not certain[] if the
symptoms are associated with the vaccination, but would recommend to report it to the
registry.” (Id.)

On June 27, 2013 petitioner consulted with pediatric neurologist Marcel Deray,
M.D. (Ex. 7, p. 126.) The history of petitioner’s present illness noted that her
narcolepsy symptoms “[s]tarted with insomnia in April 2013.” (Id.) Dr. Deray noted that
petitioner saw her primary care provider on May 1, 2013 for a routine visit and was
started on 3 mg of melatonin. (Id.) Dr. Deray also noted that petitioner received a
“Gardasil [sic] shot and another Hep A vaccine” during that visit. (Id.) Dr. Deray
remarked that petitioner’s left leg buckled three days after her vaccinations, the
“[f]ollowing day speech was slurred,” and “[f]ive days after the shot, at dinner, [her] right
arm would shake.” (Id.) Dr. Deray’s impression was narcolepsy with cataplexy
syndrome and petitioner was prescribed Ambien. (Id. at 129.) Petitioner’s mean sleep
latency test (“MSLT”) conducted in June of 2013 recorded REM onset sleep periods at
5/5 and an msl of 1.6 min., although a follow-up study in August of 2013 was normal.
(Ex. 7, pp.110, 138.)

On October 17, 2013 petitioner returned to see Dr. Dubrovsky, who confirmed
petitioner’s diagnosis of narcolepsy cataplexy syndrome. (Ex. 11, p. 104.) In this visit,
Dr. Dubrovsky noted that petitioner’s “mother [] want[ed] to clarify the history, the
[petitioner] started having difficulty staying asleep and taking daytime naps since mid-
April. She had Gardasil shot on 5/1/13 and since then developed sleep attacks and
cataplexy that was debilitating.” (Id. at 103.) Dr. Dubrovsky suggested scheduled naps
and continued petitioner’s prescriptions for Ambien and Concerta. (Id. at 103-104.)

Petitioner was later prescribed Xyrem for her narcolepsy, and continued
treatment with Dr. Deray throughout the rest of 2013 and until March 2016. (See Ex. 9,
pp. 2-10.) As of December 2019, petitioner was seeing pulmonologist Samuel
Gurevich, M.D., regarding treatment for excessive daytime somnolence, narcolepsy,
and parasomnias. (Ex. 53, p. 24.) Petitioner’s most recent records, from July 23, 2020,
indicate that she is participating in weekly psychotherapy for reasons unrelated to the
condition at issue in this case. (Ex. 54, p. 1.)

a. Petitioner’s Mother’s Affidavits

In her first affidavit, petitioner’s mother avers that petitioner received the Gardasil
vaccine and “sustained Narcolepsy cataplexy syndrome, which was actually caused by
the vaccine received.” (Ex. 10, p. 1.) In response to Special Master Millman’s order,
petitioner’s mother provided a supplemental affidavit, explaining the inconsistences in
petitioner’s medical records. (Ex. 13.)

In her second affidavit, petitioner’s mother states that “[t]here was nothing wrong
with [petitioner] on May 1, 2013” during her well-child visit and petitioner had “no

8
medical problems that day.” (Ex. 13, p. 1.) Petitioner’s mother also claims that she “did
note that [petitioner] was not sleeping,” and “[p]rior to that visit, [petitioner] had had a
work up for sleep apnea[.]” (Id.) According to petitioner’s mother, petitioner had recently
stopped playing soccer and “[she] felt at the time that the sleep issues were related to a
lack of exercise which would result in being less tired at bed time.” (Id.) She added that
this visit was “entirely a routine check-up and [] [petitioner] was cleared for participation
in athletics at its conclusion.” (Id.)

Petitioner’s mother avers that the history of present illness recorded in
petitioner’s hospital discharge record from May 16, 2013 appears to be “an accurate
narrative of what I remember to be the time line of events before and after May 1,
2013.” (Ex. 13, p. 1-2 (citing Ex. 11, p. 2).) Prior to May 1, 2013, petitioner’s mother
claims that “the only noteworthy issue involving [petitioner’s] health was her problems
falling asleep.” (Id. at 2.) However, she states that “that issue was NOT what brought
us to the pediatrician that day. In fact, as [she] reported on May 11, the character of []
[petitioner’s] sleep issues changed dramatically in the week before May 11.” (Id.)

Petitioner’s mother also avers that she has “no independent memory of saying
that [petitioner’s] narcolepsy/cataplexy symptoms began in April,” and that “at the time
of the May 11 admission [of petitioner to the hospital],” petitioner’s mother “felt that her
symptoms began after the May 1 Gardasil vaccine.” (Ex. 13, p. 2 (citing Ex. 11, p. 31).)
She is unsure “where the individual who wrote that history got the April dates
referenced,” and she does not believe that “[she] would have made the mistake of
saying that the symptoms had begun in April.” (Id.) Regardless, her mother states that
petitioner’s symptoms did not start until after May 1. (Id.)

Petitioner’s mother further avers that the history given to Dr. Gilderman
Neidenberg on May 11, 2013 which “suggests that [petitioner’s] narcolepsy/cataplexy
symptoms started in early April 2013” was in fact “wrong.” (Ex. 13, p. 2 (citing Ex. 4, p.
52.).) Additionally, petitioner’s mother asserts that the history written by Dr. Randel
during her daughter’s well-child visit on May 1, 2013, and the history given by Dr. Lazar
at discharge “reflect what [she] remember[s] about the onset of [petitioner’s]
narcolepsy/cataplexy.” (Ex. 13, p. 2 (citing Ex. 11, pp. 2, 52-56).) Though the record
suggests that she took petitioner to her primary care physician on May 1 “because of
worsened narcolepsy symptoms,” petitioner’s mother states that she did not. (Ex. 13, p.
3.) She maintains that petitioner’s May 1 visit “was a well-child visit only.” (Id.)

IV. Expert Opinions

a. Petitioner’s expert, Lawrence Steinman, M.D., initial report

Dr. Steinman received his medical degree from Harvard in 1973. He is currently
a professor of the department of neurology at Stanford University. (Ex. 14, p. 1.) Dr.
Steinman has treated patients, both adults and children, who suffered from various
forms of autoimmune disease of the nervous system, including optic neuritis, ADEM,
Bechet’s disease, inflammatory neuropathy, transverse myelitis, neuromyelitis optica

9
(NMO), and multiple sclerosis (MS). (Id.) Dr. Steinman’s research focuses on how the
immune system attacks the nervous system and he has published on the subject of
narcolepsy. (Id. at 1-3.) He holds over 50 American and European patents, including
several U.S. patents relating to vaccines. (Id. at 5.)

Dr. Steinman opines that petitioner’s HPV vaccination on May 1, 2013 “caused a
significant aggravation of a sleep disorder, leading to narcolepsy that was explicitly
diagnosed two weeks thereafter.” (Ex. 14, p. 1.) Dr. Steinman’s theory on how the HPV
vaccination “trigger[ed] narcolepsy” relies on the principles of molecular mimicry. (Id. at
9.) According to his theory, the Gardasil vaccine 10 contains molecular mimics of
hypocretin, also called orexin 11, and hypocretin-2 receptor, also known as the orexin-2
receptor. (Id.) Dr. Steinman notes three groups who have “reported immune responses
to hypocretin reception 2 in narcolepsy”: (i) a group led by Dr. Steinman who found that
“in vaccine-induced narcolepsy, there are antibodies to HCRT-R2” and who identified a
region of the HCRT-R2 molecule located at the site where hypocretin binds the
receptor12 (ii) a group in Japan which found antibodies to HCRT-R2 in narcolepsy13 and
(iii) as did a group from Oxford. 14 (Id. at 10.) Dr. Steinman also mentions a fourth
group, Mignot’s group, who showed “some evidence of antibodies to HCRT-R2 in
narcolepsy,” though he discounts these findings due to a “major flaw” in one of the
assays for HCRT-R2 that appears in their supplementary data. (Id. (citing (citing De la
Herrán-Arita et al., CD4+ T cell Autoimmunity to Hypocretin/Orexin and Cross-Reactivity
to a 2009 H1N1 Influenza A Epitope in Narcolepsy, 5(216) SCI. TRANSL. MED. 1-13
(2013) (Ex. 25); De la Herrán-Arita et al., CD4+ T cell Autoimmunity to
Hypocretin/Orexin and Cross-Reactivity to a 2009 H1N1 Influenza A Epitope in
Narcolepsy, 5(216) SCI. TRANSL. MED. 1-13 (2013) (Retraction published on July 30,
2014) (Ex. 26)).)

10Petitioner received the Gardasil Quadrivalent HPV vaccine on May 1, 2013, which contains the L1
proteins from four different strains of HPV: HPVs 6, 11, 16, and 18. (Ex. 14, p. 9 (citing Ex. 21)).
Presently, “Gardasil-9 (Merck), a nine-valent HPV vaccine (9vHPV) that protects against HPV types 6, 11,
16, 18, 31, 33, 45, 52, and 58, is the only HPV vaccine currently distributed in the U.S.” What Ty[es of
HPV Vaccines Are There?, CDC, https://www.cdc.gov/vaccines/vpd/hpv/public/index.html (last updated
Mar. 17, 2020).

11 “Either of two neuropeptides (orexin A and orexin B) produced in the hypothalamus and regulating
feeding behavior as well as the sleep-wake cycle.” Orexin, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=13359 (last visited Sept. 8, 2021).

12 Ahmed et al., Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2,7

(294) SCI. TRANSL. MED. (2015) (Ex. 27). Dr. Steinman notes that his group identified the region of the
HCRT-R2 molecule that was previously identified at the University of Texas Southwestern Medical
School, “precisely at the site where hypocretin binds the receptor.” (Ex. 14, p. 10) (citing Yin et al,
Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptions, 23(4) NAT.
STRUCT. MOL. BIOL. 293-9 (2016)).)

13 Tanaka et al., Detection of autoantibodies against hypocretin, hcrtr1, and hcrtr2 in narcolepsy: anti-hcrt

system antibody in narcolepsy, 29(5) SLEEP 633-638 (2006) (Ex. 29).
14 Giannocarro et al., Antibodies against HCRT-R2 are rare in narcolepsy, 40(2) SLEEP (2017) (Ex. 30.)

10
 Dr. Steinman carried out BLAST15 searches to identify homologies between the
components of the Gardasil vaccine and various components of the hypocretin
pathway, including hypocretin itself and the HCRT-R2 receptor. (Ex. 14, p. 11.) Dr.
Steinman classifies his criteria for a “meaningful molecular mimic” as a run of 5 or more
of 12 amino acids that are identical. (Id.) Based on his own published research, Dr.
Steinman opines that the identity of 5 of 12 amino acids, or sometimes even 4 or 11
amino acids, were sufficient to “trigger experimental neuroinflammation with paralysis.”
(Id. (citing Gautam et al, A polyalanine peptide containing only five native myeline basic
protein residues induces autoimmune encephalomyelitis, 127 JOURNAL OF EXPERIMENTAL
MEDICINE 605-609 (1992) (Ex. 32); Gautam et al., Minimum structural requirements for
peptide presentation by major histocompability complex class II molecules: Implications
in induction of autoimmunity, 91 PROC. NATL. ACAD. SCI. USA 767-771 (1994) (Ex. 33);
Gautam et al., A viral peptide with limited homology to a self-peptide can induce clinical
sign of experimental autoimmune encephalomyelitis, 161 J. IMMUNOL., 60-64 (1998) (Ex.
34)).) He also adds that the 5/12 or 4/11 amino acids that are identical need not be
consecutive. (Id.)

Through his BLAST searches, Dr. Steinman identified several homologies
between the human protein (hypocretin and hypocretin-2 receptor) and the HPV
proteins that were 5/12 or better. (Ex. 14, pp. 14-25.) Dr. Steinman acknowledges that
his report only includes the “positive” or “relevant” searches, though “[m]any searches
were performed where the criterion” were not met. (Id. at 25.) In support of his theory,
Dr. Steinman cites a paper by Ufret-Vicenty et al., whose experiments passively
transferred T cells that cross-reacted with myelin basic protein and HPV (in mice) and
found that the experimental animals became paralyzed. (Id. at 25-26 (citing Ufret-
Vincenty et al., In Vivo Survival of Viral Antigen—specific T Cells that Induce
Experimental Autoimmune Encephalomyelitis, 188 JOURNAL OF EXPERIMENTAL MEDICINE
1725-1738 (1998) (Ex. 35)).) However, it is not possible to test petitioner for immunity
to these mimics. (Id. at 26.)

Dr. Steinman acknowledges that “[m]olecular mimicry may indeed be
widespread.” (Ex. 14, p. 26.) He explains “[o]ther genetic and environmental factors”
are necessary before these self-reactive immune responses to HCRT-R2 may trigger an
immune response. (Id. at 28-29.) He maintains that his theory of molecular mimicry,
nonetheless, is a “key mechanism” in understanding how the vaccination may cause
injury. (Id.)

In response to Court Exhibit 1, Dr. Steinman suggests that this epidemiological
study, in fact, shows an increased rate of narcolepsy among those who received the
Gardasil vaccine. (Ex. 14, p. 29.) According to Dr. Steinman, the 2.61 cases of

15 According to its own website, the Basic Local Alignment Search Tool (BLAST) “finds regions of local

similarity between sequences. The program compares nucleotide or protein sequences to sequence
databases and calculates the statistical significance of matches. BLAST can be used to infer functional
and evolutionary relationships between sequences as well as help identify members of gene families.”
See https://blast.ncbi.nlm.nih.gov/Blast.cgi (last visited Dec. 2, 2021).

11
narcolepsy per 105 in the vaccinated group versus the 1.81 cases per 105 in the
unvaccinated group indicates that the Gardasil vaccine is associated with a higher rate
of narcolepsy compared to the unvaccinated, “even though it may not reach so-called
‘statistical significance.’” (Id. at 31.)

Finally, Dr. Steinman opines that petitioner’s HPV vaccination on May 1, 2013,
“changed the trajectory of the case.” (Ex. 14, p. 31.) Dr. Steinman remarks that
“though there were symptoms prior to the May 1, 2013 immunization, there was clear
worsening about 10 days after the May 1, 2013, Gardasil shot.” (Id.) Dr. Steinman
quotes the “history of present illness” in Dr. Lazar’s discharge summary from May 16,
2013:

Over the past 3 days she reports to “twitching” of her left upper extremity
and left leg lasting for approximately 20 seconds followed by a tingling
sensation in her hands. She would have approximately 2 episodes per day.
During these “twitching” episodes she would be fully awake and states that
she would use her right hand to hold on to her left upper extremity while it
was jerking but this would not stop the jerking movements. She also reports
recent episodes of light headedness and fell twice 2 days ago and once
today.

(Id.)

Dr. Steinman stresses that “[t]his type of activity was NOT present prior to the
May 1, 2013, immunization, based on the contemporaneous record.” (Id.) (emphasis in
original). According to Dr. Steinman, the progression of petitioner’s symptoms is
consistent with the progression of narcolepsy in patients studied in Finland and England
who received the Pandemrix vaccination. (Id. at 32 (citing Partinen et al., Increased
Incidence and Clinical Picture of Childhood Narcolepsy following the 2009 H1N1
Pandemic Vaccination Campaign in Finland, 7 PLOS ONE e33723 (2012) (Ex. 38);
Winstone et al., Clinical features of narcolepsy in children vaccinated with AS03
adjuvanted pandemicA/H1N1 2009 influenza vaccine in England, 56 DEV. MED. CHILD.
NEUROL. 1117-1123 (2014) (Ex. 39).)

b. Respondent’s expert, Maryann Deak, M.D., initial report

Dr. Deak received her medical degree from Georgetown University School of
Medicine in 2004. (Ex. B.) Dr. Deak currently serves as the Associate Medical Director
in Sleep Medicine for eviCore Healthcare. (Ex. A.) Dr. Deak is board certified in both
neurology and sleep medicine, with significant clinical experience treating sleep
disorders, including narcolepsy and other hypersomnia. (Id.) She completed a clinical
and research fellowship in sleep medicine at Brigham and Women’s Hospital and
Harvard Medical School in 2010. (Id.)

Dr. Deak opines that the presence of narcolepsy symptoms prior to vaccination,
the evolution of petitioner’s symptoms consistent with pediatric narcolepsy, and the lack

12
of evidence supporting an increased risk of narcolepsy with Gardasil, taken together,
show no causal link between the Gardasil vaccination and petitioner’s narcolepsy. (Ex.
A.) Both Drs. Steinman and Deak agree that petitioner developed symptoms of
narcolepsy prior to petitioner’s May 1, 2013 vaccination. (Ex. 14, p. 31; Ex. A, p. 4.) Dr.
Deak notes that petitioner presented with symptoms of sleep disruption and daytime
sleepiness with prolonged napping 4-6 weeks prior to her hospitalization. (Ex. A, p. 4
(citing Exs. 3, 4).) While petitioner’s symptoms of sleep paralysis, cataplexy, slurred
speech and gait difficulties appeared 2-4 weeks prior to hospitalization. (Ex. A, p. 4.)

Dr. Deak explains that the full narcoleptic tetrad of symptoms–excessive daytime
sleepiness, cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis–is
rarely present at initial presentation. (Ex. A, p. 5.) The order in which symptoms appear
can also vary. (Id. (citing Dauvilliers et al., Narcolepsy with Cataplexy, 369 THE LANCET
499-511 (2007) (Ex. H)).) Due to the “insidious onset” of narcolepsy, as well as
accompanying behavioral, metabolic, and mood symptoms, narcolepsy is often
misdiagnosed. (Ex. A, p. 5.) Dr. Deak notes that in more than 80% of cases cataplexy
develops within two to three months; disturbed night sleep is reported in more than 90%
of narcolepsy type 1 patients; and more than 70% of patients report a decrease in
academic performance. (Ex. A, pp. 5-6 (citing Dauvilliers et al., supra, at Ex. H. p. 499-
511).); Aran et al., Clinical and therapeutic Aspects of Childhood Narcolepsy-Cataplexy:
a Retrospective Study of 51 Children, 33 SLEEP 1457 (2010) (Ex. I).)

Dr. Deak likewise notes that narcolepsy is caused by hypocretin deficiency, likely
due to the selective loss of hypocretin-producing neurons in the hypothalamus. (Ex. A,
p. 6.) She adds that the autoimmune hypothesis is the leading theory for narcolepsy
type 1, due to a strong association between narcolepsy type 1 and the human leukocyte
antigen (HLA) DQB1*0602. (Id.) Dr. Deak also notes that (i) seasonal differences in
narcolepsy incidence, (ii) the rise in incidences post 2009-2010 administration of the
AS03-adjuvanted H1N1 vaccine and (iii) the association with anti-streptococcal
antibodies all support the theory that environmental factors contribute to the
development of narcolepsy in patients who are genetically susceptible. (Id. citing
Postiglione et al., the Clinical Spectrum of Childhood Narcolepsy, 5 SLEEP MED. REV.
70-85 (2018) (Ex. K)).) However, unlike Dr. Steinman, Dr. Deak stresses that
“autoantibodies specific to hypocretin peptides have not been found,” and to date, direct
evidence supporting the autoimmune hypothesis is lacking. (Id. (citing Mignot,
Narcolepsy: Genetics, Immunology, and Pathophysiology, in Principles and Practice of
Sleep Medicine (6th ed. 2017) (Ex. O)).)

Dr. Deak questions Dr. Steinman’s causation theory, suggesting that Dr.
Steinman relies upon data from autoimmune disorders such as multiple sclerosis and
other vaccines such as H1N1 – without presenting a causal link to Gardasil or
narcolepsy. (Ex. A, p. 7.) Dr. Deak acknowledges the increased incidence of
narcolepsy after the administration of the AS03-adjuvanted H1N1 vaccine in several
European countries. (Id.) Yet, Dr. Deak stresses that there is no increased risk of
narcolepsy with either H1N1 vaccines that contained other adjuvants, such as Focetria,
or among non-adjuvanted H1N1 vaccines given in the United States. (Id. (citing

13
Partinen, Narcolepsy as an Autoimmune Disease: the Role of H1N1 Infection and
Vaccination, 13 THE LANCET 600-13 (2014) (Ex. E); Duffy et al., Narcolepsy and
Influenza A (H1N1) Pandemic 2009 Vaccination in the United States, 83 NEUROL. 1823-
30 (2014) (Ex. Q); Nguyen et al., Vaccine-Associated Inflammatory Disease of the
Central nervous System: Form Signals to Causation, 29 CURR. OPIN. NEUROL. 1-10
(2016) (Ex. R).)

Lastly, Dr. Deak contends that Court Exhibit 1, the Arnheim-Dahlstrom et al.
study does not demonstrate any significant association between narcolepsy and HPV
vaccination. (Ex. A, p. 7.) Quoting the authors in that study, Dr. Deak notes that “this
large cohort study found no evidence supporting associations between exposure to
HPV vaccine and autoimmune, neurological, and venous thromboembolic adverse
events.” (Id. (citing Arnheim-Dahlstrom et al., Autoimmune Neurological, and Venous
Thromboembolic Adverse Events After Immunisation of Adolescent Girls with
Quadrivalent Human Papillomavirus Vaccine in Denmark and Sweden: Cohort Study,
347 Brit. Med. J. 1-11 (2013) (Ex. S.))

c. Respondent’s expert, J. Lindsay Whitton, M.D., Ph.D., initial report

Dr. Whitton received his medical degree from the University of Glasgow in 1979
and his doctorate degree in virology (focusing on herpesvirus transcription) also from
the University of Glasgow in 1984. (Ex. D.) Dr. Whitton has not sought licensure in the
United States, nor has he practiced medicine in the United States. 16 (Ex. C.) As of the
time of his submissions in this case, Dr. Whitton serves as a professor in the
Department of Immunology and Microbiology at the Scripps Research Institute. (Ex. D.)
He has published extensively on the adaptive and innate immune response and on
molecular mimicry. (Id.)

Dr. Whitton likewise agrees with Drs. Steinman and Deak that the onset of
petitioner’s disease preceded the vaccination. (Ex. C, p. 3-4.) Dr. Whitton disagrees
with Dr. Steinman’s opinion that the HPV vaccine “changed the trajectory of the case”
and would be a “significant aggravation.” (Id. at 4 (citing Ex. 14, p. 6.)) Rather, Dr.
Whitton opines that petitioner’s disease severity “was clearly increasing prior to, or
contemporaneous with, the vaccination.” (Ex. C, p. 4.) Like Dr. Deak, Dr. Whitton finds
that the onset and progression of petitioner’s symptoms are consistent with the typical
evolution of pediatric narcolepsy. (Id.)

Additionally, Dr. Whitton opines that there is no significant association reported
between narcolepsy and the HPV vaccine. Dr. Whitton believes that Dr. Steinman’s
reliance on various studies of the Pandemrix vaccine and narcolepsy is misplaced. (Ex.
C, pp. 4, 12-13.) According to Dr. Whitton, Dr Steinman attempts to “tar Gardasil using
the Pandemrix brush.” (Id. at 5.) Dr. Whitton stresses that Dr. Steinman’s theory is “not

16In his report Dr. Whitton notes that while he is “medically qualified,” he has never sought licensure in
the United States, and he shall defer to Dr. Deak’s expertise in the area of sleep disorders and
diagnoses. (Ex. C at 2.)

14
scientifically appropriate; one cannot reasonably infer that what may happen with one
vaccine must happen with all vaccines.” (Id.) (emphasis in original.)

With regard to causation, Dr. Whitton opines that Dr. Steinman’s molecular
mimicry theory is not a valid causal theory for the development, or exacerbation of,
narcolepsy. Dr. Whitton takes issue with Dr. Steinman’s classification of a “meaningful
molecular mimic.” (Ex. C, p. 5.) First, he explains that in order to identify an amino acid
sequence as a “mimic,” one cannot rely on a shared homology alone. (Id.) Mimicry is
defined by the “immune response that the sequence induces” and to be a “mimic” the
amino acid sequence must “(i) [] trigger an immune response and, (ii), that response
must recognize (i.e., cross-react with) the other peptide[.]” (Id.) (emphasis in original).
Unless both criteria are met, then it is not a mimic, but merely a homology. (Id.)

With respect to Dr. Steinman’s BLAST searches, Dr. Whitton notes that for the
L1 protein of HPV11 and hypocretin, he found seven additional homologies of 5/12 or
better; and for hypocretin receptor 2 and L1 protein HPV18, he found twenty-three
additional homologies of 5/12 or better. (Ex. C, p. 6.) According to Dr. Whitton these
additional “hits,” demonstrate that Dr. Steinman’s rare and “meaningful molecular
mimics” are in fact commonplace and not meaningful. (Id.) Even statistical probability
demonstrates how the presence of numerous homologies is entirely predictable among
a large number of proteins. 17 (Id. at 7-10.)

Dr. Whitton also stresses that most homologies do not trigger biologically-
meaningful cross-reactivity. (Ex. C, p. 11.) Dr. Whitton compared two of the L1 proteins
from HPV6 and HPV 11 and found 487 homologies of 5/12 or better. (Id.) Following Dr.
Steinman’s logic, Dr. Whitton suggests that every one of these 487 homologies should
trigger cross-reactive immunity. (Id.) And if each one of these 487 responses were
“meaningful,” Dr. Whitton explains, the immune response against the HPV6 L1 protein
“should confer protection against both the parental virus (HPV6) and the other virus
(HPV11).” (Id.) If this were the case, the HPV vaccine would require only one of the
viral proteins to induce immune responses that would protect against both viruses. (Id.)
“But, of course, this isn’t the biological reality.” (Id.) Dr. Whitton therefore concludes
that even when there are 487 homologies, it would be wrong to conclude that one of
them must have a meaningful biological impact. (Id.) Studies such as Trost et al.,
which compared bacterial proteins against the human proteome identified thousands of
short homologies. (Id. (citing Trost et al., Bacterial peptides are intensively present
throughout the human proteome, 1 SELF NONSELF 71-74 (2010) (Ex. U)).) Dr. Whitton
stresses that molecular mimicry is “real,” however, the mere existence of a homology is
insufficient to trigger an immune-mediated disease. (Id.)

Dr. Whitton notes that large studies have failed to identify any causal relationship
between the HPV vaccine and several autoimmune diseases. (Ex. C, p. 12.) Dr.

17 Dr. Whitton explains, in part, “[i]t’s like being given a lottery ticket, and being told that there is a

1/32,000 chance of its being a winning ticket. You wouldn’t be too excited. But if a truck delivered another
218,239 tickets to your doorstep, you’d be ecstatic.” (Ex. C, p. 8.)

15
Whitton cites only one published scientific study which in his estimation suggests that
the HPV vaccine may have autoimmune consequences. (Id. at 13 (citing Andrews et
al., No Increased Risk of Guillain-Barre Syndrome After Human Papilloma Virus
Vaccine: a Self-Controlled Case-Series Study in England, 35 VACCINE 1729-1732
(2017) (Ex. AA)).) Yet, he finds that the association was weak, the paper did not use
clinician-validated cases of the disease and did not find any association with GBS. 18
(Id.) Turning to the HPV vaccine, Dr. Whitton cites a 2018 review which states:

We identified 109 studies, including 15 population-based studies in over
2.5 million vaccinated individuals across six counties. All vaccines
demonstrated an acceptable safety profile; injection-site reactions were
slightly more common for 9vHPV vaccine than for 4vHPV vaccine. There
was no consistent evidence of an increased risk of AESI 19, including
demyelinating syndromes or neurological conditions such as
complex regional pain or postural orthostatic tachycardia syndromes.
The risk-benefit for HPV vaccines remains highly favourable.

(Id. (citing Phillips et al., Safety of Human Papillomavirus Vaccines: an Updated Review,
41 DRUG SAF. 329 (2018) (Ex. CC)) (emphasis in original).

Dr. Whitton likewise notes that the authors of the Arnheim-Dahlstrom et al.
study–which evaluated the frequency of several diseases (including narcolepsy)
appearing within a 180-day window following HPV vaccination–concluded “no significant
association was observed with narcolepsy.” (Ex. C, p. 14) (quoting Arnheim-Dahlstrom
et al., supra, at Ex. S, p. 5 (2013)).) Dr. Whitton notes that Dr. Steinman’s analysis of
this study “ignore[s]” the statistical significance of the results, in favor of the absolute
number of cases of narcolepsy in those vaccinated versus unvaccinated. (Ex. C, p. 14.)

d. Dr. Steinman’s first supplemental report, Exhibit 40

In his first supplemental report, Dr. Steinman highlights the development of
“twitching episodes” a few days prior to petitioner’s May 11 admission as a new
symptom that developed after petitioner’s HPV vaccination. (Ex. 40, pp. 2-3.)
Additionally, Dr. Steinman reiterates that the worsening of petitioner’s symptoms over a
12-month period is consistent with studies involving narcolepsy and the H1N1 vaccine
in England and Sweden. (Id. at 3 (citing Partinen et al., supra, at Ex. 38; Winstone et
al., supra, at Ex. 39).) Dr. Steinman proposes that the Arnheim-Dahlstrom et al. study,
Court Exhibit 1, “does reinforce the Petitioner’s theory to the level of a ‘preponderance
of evidence.’” (Ex. 40, p. 7.) In the context of what Dr. Steinman describes as a
“meaningful metric when the burden of proof is described as 50% and a feather,” he

18 Dr Whitton writes “[o]bviously, GBS is not claimed in the present matter. However, to my knowledge,

this is the only published scientific study to suggest that HPV vaccine may have any autoimmune
consequences whatsoever and, as such, it is worthy of a little dissection.” (Ex. C, p. 13.)

19 “AESI = adverse event of special interest” (Ex. C, p. 13)

16
suggests that the 2.4-fold increase in the upper limit for Gardasil vaccinated versus
unvaccinated is significant. (Id. at 6-7.)

In response to criticism of his molecular mimicry theory, Dr. Steinman quotes a
passage from one of Dr. Whitton’s papers, in part, “showing that almost 4% of antiviral
monoclonal antibodies also reacted with self proteins.” (Ex. 40, p. 9 (citing Fujinami et
al., Molecular Mimicry, Bystander Activation, or Viral Persistence: Infections and
Autoimmune Disease, 19(1) CLIN. MICROBIOL. REV. 80-94, 81 (2006) (Ex. 41).) Dr.
Steinman explains that “[i]f 4% of viral antibodies reacted with self-proteins, it is
expected that over the life of a human subjected to viral infections, that there would be a
large component of anti-viral antibodies that are also ‘anti-self.’” (Ex. 40, p. 9.)
Following this logic, Dr. Steinman stresses that autoimmunity is in fact widespread. (Id.)

Dr. Steinman explains that his references to the Pandemrix vaccine provided
background, and his theory in regard to petitioner’s case is based on “how the contents
of the Gardasil vaccine share structural similarities with molecules that are key in
narcolepsy, orexin (hypocretin) and its receptor.” (Ex. 40, p. 9.) Furthermore, Dr.
Steinman disputes Dr. Whitton’s “simple math,” and instead proposes that “these
homologies are NOT inevitable.” (Ex. 40, p. 10.) As evidence Dr. Steinman provides
examples of his positive searches (where he identifies a homology) and negative
searches (where he failed to identify a homology of an acceptable degree.) (Id. at 10-
12.) With these searches Dr. Steinman appears to suggest that when a homology is
identified (a positive search) it is therefore biologically-significant.

In response to Dr. Whitton’s results (identifying 487 homologies of 5/12 or better
between HPV6 and HPV11) Dr. Steinman explains that these two strains “are closely
related.” (Ex. 40, p. 12.) Finding a match between these two strains is “akin to
marveling at how similar are members of a biologic family,” according to Dr. Steinman.
(Id.) He explains that what is significant is that HPV6 and HPV11 have “mimics of
significance” with orexin, while there are no matches for HPV16 and HPV18 (though all
four L1 proteins, HPV6, HPV11, HPV16 and HPV18, are present in the Gardasil
vaccine). (Id.)

Dr. Steinman also suggests the presence of alum makes the HPV components
more immunogenic. (Ex. 40, p. 13.) As a result, “[t]he Gardasil vaccine leads to a 40-
fold increase in HPV antibodies compared with the physiological antibody level triggered
by a natural HPV infection.” (Id. (quoting Souayah et al., Guillain-Barre Syndrome after
Gardasil vaccination: Data from Vaccine Adverse Event Reporting System 2006-2009,
29 Vaccine 886-889 (2011) (Ex. 42).) Dr. Steinman appears to suggest that the alum
adjuvant increases the probability that a cross-reactive immune response may be
induced.

e. Dr. Deak’s first supplemental report, Exhibit GG

In her supplemental report, Dr. Deak opines that “[a] vaccine given in the midst of
typical symptom evolution does not constitute a causal relationship.” (Ex. GG, p. 1.)

17
While Dr. Steinman highlights the presence of hand twitching a few days prior to
petitioner’s admission as a new symptom that she developed post-vaccination, Dr. Deak
explains that cataplexy may present differently in children than in adults. (Id.) Cataplexy
in children may not be linked to emotional stimuli and may present as loss of muscle
tone or increased motor movements. (Id. (citing Nevsimalova, The Diagnosis and
Treatment of Pediatric Narcolepsy, 14 CURR. NEUROL. NEUROSCI. Rep. 469 (2014) (Ex.
G); Postiglione et al, supra, at Ex. K).) Furthermore, Dr. Deak reiterates that petitioner
was already experiencing symptoms suggestive of cataplexy prior to her vaccination.
(Id.) That certain symptoms manifested as petitioner’s narcolepsy progressed “is only
evidence of the expected progression and does not constitute significant aggravation of
her underlying disease course.” (Id. at 1-2.)

Dr. Deak also takes issue with Dr. Steinman’s theory of a greater-than-12-month
narcolepsy onset. (Ex. GG, p. 2.) In the first article Dr. Steinman cites from Finland, Dr.
Deak points out that the status and date of Pandemrix vaccination was obtained from
vaccination certificates filed by health care professionals in Finland and the presence of
narcolepsy symptoms and time of onset were retrospectively obtained from the medical
records. (Id. (citing Partinen et al., Increased incidence and clinical picture of childhood
narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland, 7
PLOS ONE e33723 (2012) (Ex. HH)).) That study reported a mean interval of 53 days
from the date of vaccination to the onset of symptoms – for children aged 17 or
younger. (Id.) Furthermore, Dr. Deak notes that the study from England that Dr.
Steinman cites is also a retrospective review, where vaccination status and time of
onset was determined by questionnaires sent to general practitioners. (Id. (citing
Winstone et al., supra, at Ex. 39).) In that study, Dr. Deak highlights that only eleven
children received the Pandemrix vaccine prior to the onset of symptoms of narcolepsy,
while seven of the eleven children received the vaccine six months or less prior to the
reported onset of symptoms, and six children received the vaccine within three months.
(Ex. GG, p. 2.) Generally, Dr. Deak notes that the reported timing of symptom onset is
prone to recall bias. (Id.) Based on her own clinical experience, and the insidious
nature of narcolepsy onset, Dr. Deak stresses that the onset of symptoms in a
retrospective study is likely to have occurred prior to the reported time of presentation.
(Id.)

Dr. Deak cites a retrospective study conducted in Sweden where symptom onset
was determined based on medical record review and telephone interviews with parents
and patients. (Ex. GG, p. 2 (citing Attila Szakacs et al., Increased childhood incidence
of narcolepsy in western Sweden after H1N1 influenza vaccination, 80 NEUROLOGY,
1315-1321 (2013) (Ex. II)).) In that study, the median time from H1N1 vaccination to
symptom onset was nine and a half weeks, with nineteen of the twenty-eight patients
developing symptoms in twelve weeks or less. (Id.) Additionally, Dr. Deak cites a study
in Norway where onset was defined by reports from physicians based on interactions
with parents or patients; and in that study the median time from vaccination to onset
was eleven weeks, with forty-two of the fifty-eight patients experiencing clinical
symptoms within six months of vaccination. (Id. (citing Heier et al., Incidence of
narcolepsy in Norwegian children and adolescents after vaccination against H1N1

18
influenza A, 14 SLEEP MEDICINE 867-871 (2013) (Ex. JJ)).) Dr. Deak notes that this
study found “no significant difference in the incidence of narcolepsy during the second
year after vaccination compared to unvaccinated children in the same time period.” (Id.)
In light of these studies, Dr. Deak “[do[es] not agree that causation can be inferred with
a greater than one year time interval between vaccination and the development of
symptoms in H1N1.” (Id.)

Nor does Dr. Deak believe that the HPV vaccine is analogous to the H1N1
vaccine. (Ex. GG, p. 3.) She emphasizes that there is no literature demonstrating an
increased incidence of narcolepsy with the HPV vaccine administered in this case. (Id.)
Dr. Deak disagrees with Dr. Steinman’s claim that results that are not statistically
significant are still consistent with “a greater than 50% likelihood” that there is a
relationship between HPV vaccination and development of narcolepsy. (Id.) Dr. Deak
stresses that without a significant association, reviewing experts cannot determine
whether there is any difference in narcolepsy incidence between unvaccinated and
vaccinated individuals in this study. (Id.)

f. Dr. Whitton’s first supplemental report, Exhibit EE

In his first supplemental report, Dr. Whitton echoes Dr. Deak’s opinions on the
Arnheim-Dahlstrom et al. study. (Ex. EE, pp. 1-2.) Dr. Whitton observes that the
authors in the Arnheim-Dahlstrom study did not provide the actual p value of their
findings regarding narcolepsy, but only state that there was no significant association
between vaccinated and unvaccinated groups. (Id. at 2.) Thus, Dr. Whitton explains,
Dr. Steinman’s inference regarding “95% certainty” is unjustified. (Id.) Dr. Whitton also
notes a more recent study in which the authors again studied the frequency of
narcolepsy following HPV vaccination and “again, no significant association between
the two was identified.” (Id. (citing Hvid, et al., Human papillomavirus vaccination of
adult women and risk of autoimmune and neurological diseases, 283 J. Intern. Med.
154-165 (2018) (Ex. FF)).)

Dr. Whitton also seeks to further refute the significance of Dr. Steinman’s positive
and negative BLAST searches. (Ex. EE, pp. 2-3.) Dr. Whitton explains that Dr.
Steinman’s “negative searches” are BLAST searches which failed to identify a
homology within an acceptable degree (per Dr. Steinman’s criteria, 5/12 amino acids).
(Id. at 3.) However, Dr. Whitton notes that when he replicated the same “negative”
BLAST search, comparing the same two proteins, hypocretin and the L1 protein of
HPV18, he identified thirteen homologies of 5/12 or better. (Id.) Dr. Whitton also
replicated the “negative” BLAST search for HPV16 and identified nine homologies of
5/12 or better. (Id.) These results, Dr. Whitton explains, again demonstrate that
homologies are commonplace. (Id.)

Like Dr. Steinman, Dr. Whitton agrees that there are “many perfect matches”
between the two HPV L1 proteins and that “such similarities ‘are expected.’” (Ex. EE, p.
4.) Yet Dr. Whitton suggests that the question that remains unanswered is, why then,
despite the presence of so many similarities, do these proteins not induce cross-

19
protective immune responses? (Id.) Again Dr. Whitton explains that despite the 487
homologies, the L1 protein of HPV6 does not protect against HPV11, and vice-versa.
(Id.) Thus, no biologically-relevant cross-reactivity is induced by the HPV vaccine, even
in the presence of alum as Dr. Steinman suggests. (Id.) According to Dr. Whitton, Dr.
Steinman also provides no evidence that these suspected immune responses would be
harmful. (Id.)

g. Dr. Steinman’s second supplemental report, Exhibit 43

In his second supplemental report, Dr. Steinman emphasizes that his molecular
mimicry theory demonstrates how a vaccine could cause the claimed injury; the theory
is “not based on ‘certainty,’ and thus never intended to ‘surely be biologically-
significant.’” (Ex. 43, p. 1.) Dr. Steinman cites the Latorre et al. study which he
suggests confirms his “smoking gun.” (Ex. 43, p. 2; Latorre et al., T cells in patients with
narcolepsy target self-antigens of hypocretin neurons, 562 NATURE 63 (2018) (Ex. 45).)
Dr. Steinman highlights results which discovered a T cell that responded to the
sequence MGRRAGAEPAPRP in the spinal fluid of a patient with narcolepsy. (Id. at 3.)
This cytotoxic T cell, Dr. Steinman concludes, “would have the capacity to target and kill
hypocretin neurons.” (Id.)

Dr. Steinman further remarks that the BLAST searches with hypocretin did not
identify a large number of epitopes. (Ex. 43, p. 5.) For HPV11 Dr. Steinman reports
only one region of hypocretin (a 5/10 sequence) and for HPV6 Dr. Steinman reports
three regions were identified but only the 5/10 sequence was identified as causing
experimental neuroinflammation. (Id.) The other two sequences were considered “not
to be ‘of interest.’” (Id.) According to Dr. Steinman, the “confirmation with actual
experimental data” from LaTorre indicates that the BLAST search efforts “are fruitful and
that they can definitively identify a mimic in the HPV vaccine with orexin.” (Id.)

Dr. Steinman also suggests that Dr. Whitton may not have used the alignment
algorithms of BLAST, possibly explaining the differences in their BLAST results. (Ex.
43, p. 5-8.) Given that the HPV vaccine contains a molecular mimic identified as a
target of killer T cells found in the spinal cord of narcolepsy patients, Dr. Steinman
disagrees with Dr. Deak’s conclusion that no causal relationship can be found. (Id. at
9.) Dr. Steinman also opines that if an individual, such as petitioner, receives an HPV
vaccine that “‘boosts’ immunity to orexin, even during the early onset of narcolepsy” the
vaccine could aggravate the pathologic immune response, culminating in “full blown
narcolepsy.” (Id.) Dr. Steinman reiterates his conclusions regarding the studies from
Sweden, Norway, and England; but adds that the findings from the Latorre et al. study
also support his conclusion that the administration of the HPV vaccine “could
exacerbate incipient narcolepsy and renders the studies cited by Dr. Deak on
Pandremix far less significant.” (Id. at 9-10.)

h. Dr. Whitton’s second supplemental report, Exhibit KK

In his second supplemental report, Dr. Whitton stresses that “BLAST [searches]
trade[] accuracy for speed.” (Ex. KK, p. 5.) Dr. Whitton asserts that his own sliding

20
window searches “do not have any such tradeoff.” (Id.) Rather, Dr. Whitton claims his
searches “accurately identify all instances of the sought-after homologies (e.g., 5
identities out of 12 resides), and they are by far the best way by which to identify short
homologies.” (Id.)

Dr. Whitton questions Dr. Steinman’s methodology because Dr. Steinman’s
smoking gun (RAGAEPAPRP) falls short of the Silvanovich et al. standard, which
Steinman relies upon in his own report. (Ex. KK, p. 6; Ex. 43, pp. 4-5.) The Silvanovich
standard requires “(i) a window of at least 80 amino acids in length (ii) in which there is
at least 35% amino acid identity and (iii) whose E-value 20 must be lower than 3.9 x 10-7.”
(Id. at 7 (citing Silvanovich et al., The value of short amino acid sequence matches for
production of protein allergenicity, 90 TOXICOL. SCI. 252-258 (2006) (Ex. OO);
Silvanovich et al., The use of E-scores to determine the quality of protein alignments 54
REGUL. TOXICOL. PHARMACOL. S26 (2009) (Ex. PP)).) According to Dr. Whitton, none of
Dr. Steinman’s BLAST results meet these criteria. (Id. at 6.) Moreover, a BLAST result
that meets the three Silvanovich criteria, “may provide a hint about the overall shape of
a protein” and “may provide a hint about IgE responses, but it can tell us absolutely
nothing about whether or not that sequence may trigger a T cell response.” (Ex. KK, p.
8) (emphasis in original).

According to Dr. Whitton, Dr. Steinman’s “chance finding” (RAGAEPAPRP) did
not predict the observations later made by Latorre et al. (Ex. KK, p. 12.) Dr. Whitton
frames Dr. Steinman’s theory as follows: “if ‘vaccine X’ contains a homology to Latorre’s
20 amino acid peptide, then that vaccine more likely than not causes narcolepsy.” (Id.)
To test the validity of Dr. Steinman’s theory, Dr. Whitton compared the short orexin
sequence against the measles vaccine. (Ex. KK, pp. 14-15.) Dr. Whitton identified four
homologies, and then carried out the same comparison using BLAST, and one hit was
returned, containing a 5/11 homology with an E-value of 0.17. (Id. at 15.) Dr. Whitton
explains that these results indicate that the measles vaccine, more likely than not,
triggers narcolepsy. (Id.) Yet, “[t]he MMR vaccine was introduced in 1963” and “no
association has ever been reported between MMR and narcolepsy.” (Id.) The mere
existence of a homology to the orexin sequence, therefore, does not “inculpate[] a
vaccine.” (Id.)

Dr. Whitton also remarks that narcolepsy and orexin deficiency are commonly
associated with MHC class II, which tends to impact CD4+ T cells (not CD8+ T cells).
(Ex. KK, p. 15.) Dr. Steinman notes in his report that petitioner carries the class II MHC
allele. (Id. (citing Ex. 14, p. 6.) However, Dr. Steinman’s smoking gun responds to an
epitope that is presented by MHC class I (stimulating CD8+ T cells), not by MHC class
II. (Id.) Moreover, Dr. Whitton concludes that there is no evidence that that the orexin-
peptide-responsive CD8+ T cells are the cause of the disease. (Id.) Instead, they could

20 The Expect value € is “a parameter that describes the number of hits one can “‘expect’ to see by

chance when searching a database of ap articular size.” (Ex. KK, p. 6.) See
https://blast.ncbi.nlm.nih.gov/Blast.cgi?CMD=Web&PAGE_TYPE=BlastDocs&DOC_TYPE=FAQ#expect
(last visited Sept. 1, 2021).

21
“well be the result of the disease; perhaps orexin released from damaged neurons has
induced these cells.” (Id.) (emphasis in original.)

i. Dr. Steinman’s third supplemental report, Exhibit 49

In his third supplemental report, Dr. Steinman opines that Dr. Whitton’s analysis
“‘conveniently ignore[s]’ a key amino acid or series of key amino acids.” (Ex. 49, p. 4.)
According to Dr. Steinman, Table 1 in Exhibit KK does not show whether the smoking
gun (RAGAEPAPRP) by itself would stimulate the clone found in the spinal fluid of a
narcolepsy patient because Dr. Whitton’s table lacks the terminal amino P. (Id. (citing
Sakai et al, Involvement of distinct murine T-cell receptors in the autoimmune
encephalitogenic response to nested epitopes of myeline basic protein, 85 PROC. NATL.
ACAD. SCI. USA 8608-8612 (1988) (Ex. 51)).) Without one or more critical amino acids,
Dr. Steinman stresses that Dr. Whitton’s analysis is “deeply flawed.” (Ex. 49, p. 4.)

Dr. Steinman also summarizes his search process in detail, at the request of Dr.
Whitton. (Ex. 49 pp. 5-8 (see Ex. KK, p. 7 n. J.) Dr. Steinman adds two additional steps
beyond the BLAST searches and explains that this filtration “eliminates sequences
homologies that are below a threshold that has been shown to induce
neuroinflammation.” (Ex. 49, p. 5.) Finally, Dr. Steinman adds a third filter “using the
LaTorre paper” and the Immune Epitope Database (IEDB). 21 (Id.)

j. Dr. Whitton’s final supplemental report, Exhibit RR

In his final supplemental report, Dr. Whitton likewise agrees that removing a
single amino acid can alter how a peptide is “seen” by a CD8+ T cell. (Ex. RR, p. 4.)
However, Dr. Whitton suggests that Dr. Steinman’s “missing proline” argument is
flawed. (Id. at 5.) A peptide that does not trigger CD8+ T cells does not transform into a
peptide that can stimulate CD8+ T cells simply by the addition of an amino acid. (Id.)
According to Dr. Whitton, the opposite is true. (Id.) The proper method is to “identify a
peptide that can stimulate T cells, and then [] remove peptides from either side, until you
identify the minimal number of peptides that can still activate the T cells” – known as the
minimal epitope. (Id.) (emphasis in original).

Dr. Whitton remarks that Dr. Steinman’s smoking gun is in fact “an empty barrel.”
(Ex. RR, p. 6.) He explains that peptide 13 is recognized by the CD8+ T cells, while
peptide 12 is not. (Id.) From this, Dr. Whitton opines, it is possible to conclude that the
T cells respond to peptide 13 because there are an additional 8 amino acids at the right-
hand end. (Id.) It is unclear, however, how many of those 8 amino acids are needed to
trigger the T cells. (Id.) Yet, by looking at peptide 14, which the T cells also recognize,
Dr. Whitton opines that it is possible to discard half of the smoking gun peptide without

21 The IEDB “catalogs experimental data on antibody and T cell epitopes studied in humans, non-human

primates, and other animal species in the context of infectious disease, allergy, autoimmunity, and
transplantation. The IEDB also hosts tools to assist in the prediction and analysis of epitopes.” See
https://www.iedb.org/home_v3.php (last visited Sept. 1, 2021).

22
preventing T cell recognition. (Id.) Ultimately, of the remaining half, only 2 residues are
identical between HPV L1 and orexin. (Id. at 7.)

Dr. Whitton agrees that the IEDB database is a valuable resource. (Ex. RR, p.
8.) According to Dr. Whitton, however, Dr. Steinman should have entered the vaccine
part of the homology in the IEDB database, not the sequences from the human protein
orexin. (Id. (citing Ex. 49, p. 7).) After entering Dr. Steinman’s homology into the IEDB,
Dr. Whitton reports that no match was found. (Ex. RR, p. 8.) Therefore, Dr. Whitton
concludes, Dr. Steinman’s homology in the HPV L1 protein is not known to be an
immunological epitope. (Id.)

k. Dr. Steinman’s final supplemental report, Exhibit 55

In his final supplemental report, Dr. Steinman reiterates that the epitope
RAGAEPAPRP from the BLAST search is contained in the epitope targeted by a CD8+
T cell in the spinal fluid of a patient with narcolepsy. (Ex. 55, p. 2.) Dr. Steinman
maintains his conclusion that “[t]here is a component of the vaccine that is a molecular
mimic of the orexin molecule targeted in narcolepsy.” (Id.) (emphasis in original). Dr.
Steinman also opines that the molecular mimics, along with the adjuvant in the vaccine
“could become problematic in a susceptible individual, triggering narcolepsy cataplexy
syndrome in [petitioner].” (Id. at 3.)

V. Party Positions

a. Petitioner’s contentions

Petitioner contends that the record evidence is clear in demonstrating that
petitioner’s May 1, 2013 HPV vaccination significantly aggravated the disease process
of narcolepsy. (ECF No. 73, p.1.) Petitioner asserts that, consistent with narcolepsy,
she experienced sleeplessness beginning in early April 2013, but the increase and
evolution of her symptoms were ultimately caused by the HPV vaccine. (Id. at 13-16.)

Petitioner asserts that her diagnosis of narcolepsy is not in controversy. (Id. at
7.) Petitioner contends that the medical records clearly indicate that petitioner was an
otherwise healthy child, with no complaints of neurological problems. (Id. at 17.) Ten
days after her vaccination, petitioner asserts that she presented to the hospital with new
and worsening symptoms including slurred speech, weakness, difficulty walking, muscle
twitching and significantly worsened sleep. (Id.) Dr. Steinman’s molecular mimicry
theory links the vaccination to petitioner’s subsequent significant aggravation, resulting
in her diagnosis of narcolepsy. (Id. at 19.)

Petitioner acknowledges that the results discussed in Court Exhibit 1 were not
statistically significant, nor did the authors provide the actual p value. (ECF No. 73, p.
24.) Petitioner contends that the rise in cases of narcolepsy in the unvaccinated group,
however, is evidence supporting the plausibility that petitioner’s HPV vaccine could
significantly aggravate her narcolepsy. (Id.) Petitioner also acknowledges some

23
variability in the recorded patient histories, but maintains that prior to her HPV
vaccination, petitioner only suffered awakenings at night accompanied by daytime
sleepiness. (Id. at 26.) Petitioner asserts that “[t]here is no evidence of another factor
that may have exacerbated [petitioner’s] narcolepsy.” (Id. at 26-27.)

In response to respondent’s contentions, petitioner stresses that there is
evidence in the contemporaneous records that petitioner’s symptoms dramatically
increased ten days after her vaccination. (ECF No. 76, p. 2.) Petitioner also stresses
that respondent’s reliance on the Trost et al. study is inappropriate. (Id. at 6.) Petitioner
argues that this study focuses on bacterial sequences, as opposed to viral proteins.
(Id.) In addition, petitioner contends that Dr. Steinman’s theory presents a causal link
between the HPV vaccine and narcolepsy based on T cell pathology, not antibody-
mediated dysfunction. (Id. at 7-8.) Petitioner emphasizes that the Pandemrix studies
were cited by Dr. Steinman to show a correlation of timing, not to draw comparisons
between the HPV and H1N1 vaccines. (Id. at 9.)

b. Respondent’s contentions

Respondent argues that Dr. Steinman employs an unreliable methodology and
does not cogently explain how the HPV vaccine may cause or significantly aggravate
narcolepsy through molecular mimicry. (ECF No. 75, pp. 17-18.) Respondent also
stresses that petitioner’s treating physicians do not support vaccine-causation, noting
that her neurologist noted daytime sleepiness, cataplexy and sleep paralysis were
“exacerbated after Gardasil shot.” (Id. at 18, 31.) Respondent argues this observation
only amounts to a temporal association. (Id.) Respondent further alleges that
petitioner’s reliance on epidemiological studies involving the Pandemrix H1N1 influenza
vaccine is unpersuasive. (Id. at 36.)

Respondent also contends that petitioner’s symptoms followed a typical course
of pediatric narcolepsy, and her symptoms were already progressing prior to
vaccination. (ECF No. 75, pp. 36-37.) Respondent stresses that petitioner overlooks
the fact that she has two “diagnostic markers” of narcolepsy, low levels of hypocretin in
her spinal fluid and the HLA DQB1*0602 gene. (Id. at 38.) Respondent contends that
pediatric narcolepsy diagnoses are often delayed, and the timing of petitioner’s
diagnosis “says nothing about the actual course of her disease.” (Id.) Finally,
respondent argues that any “substantial factor” claim would suffer the same limitations
with respect to establishing vaccine causation. (Id. at 41-42.)

VI. Discussion

The most extensively debated aspect of this case is the validity of petitioner’s
theory of causation explaining how petitioner’s HPV vaccine could have significantly
aggravated her condition. This presents a threshold issue in this case. Accordingly, I
will address petitioner’s theory of causation first. Having found that petitioner did not
meet her burden of proof on this point, I will then more briefly address the remaining
elements of the six-part Loving test discussed above.

24
 a. Petitioner’s Medical Theory (i.e. the Althen prong one / Loving prong
four)

Petitioner’s burden under the first Althen prong/fourth Loving prong is to provide,
by preponderant evidence, “a medical theory causally connecting the vaccination and
the injury.” Althen, 418 F.3d at 1278. Such a theory must only be “legally probable, not
medically or scientifically certain.” Knudsen v. Sec’y of Human & Health Servs., 35 F.3d
543, 548-49 (Fed. Cir. 1994). Moreover, scientific evidence offered to establish Althen
prong one is viewed “not through the lens of the laboratorian, but instead from the
vantage point of the Vaccine Act's preponderant evidence standard.” Andreu v. Sec’y of
Health & Human Servs., 569 F.3d 1367, 1380 (Fed. Cir. 2009). However, to satisfy this
prong, petitioner’s theory must be based on a “sound and reliable medical or scientific
explanation.” Knudsen, 35 F.3d at 548; Boatmon, 941 F.3d at 1359.

Petitioner’s medical theory regarding how her HPV vaccination significantly
aggravated her narcolepsy cataplexy syndrome posits an autoimmune response to the
vaccination, “targeting human proteins that are implicated in the disease process of
narcolepsy.” (ECF No. 73, p. 19.) Petitioner relies on Dr. Steinman’s theory of
molecular mimicry to link the vaccination to her subsequent significant aggravation of
narcolepsy. (Id.) Below I shall address (1) the debate as to whether narcolepsy is an
autoimmune condition and whether a relevant autoantibody has been identified; (2)
whether the epidemiologic evidence links narcolepsy to the HPV vaccine by
preponderant evidence; and (3) whether Dr. Steinman’s demonstrated homologies can
be shown to demonstrate a causal relationship between the HPV vaccine and injury.

i. Narcolepsy Type 1 and autoimmunity

Narcolepsy type 1 is a disorder characterized by excessive daytime sleepiness
and signs of REM-sleep dissociation, the most specific of which is cataplexy. (American
Academy of Sleep Medicine, Narcolepsy Type 1, International Classification of Sleep
Disorders (3d ed. 2014) (Ex. F).) Narcolepsy is caused by hypocretin deficiency, likely
due to the selective loss of hypocretin-producing neurons in the hypothalamus. (Mignot,
supra, at Ex. O.) According to Mignot, when cataplexy is present, “the cause is almost
always an immune-mediated destruction of the hypocretin-producing (also called orexin)
neurons in the hypothalamus.” (Id.) The autoimmune hypothesis is the leading theory
for narcolepsy type 1, due to a strong association between narcolepsy type 1 and the
human leukocyte antigen (HLA) DQB1*0602. (Postiglione, supra, at 70 (Ex. K).)

Respondent’s expert, Dr. Deak, acknowledges that the autoimmune hypothesis
is the leading theory for the pathophysiology of narcolepsy type 1, but stresses that
“autoantibodies specific to hypocretin peptides have not been found,” and that direct
evidence supporting the autoimmune hypothesis is lacking. (Ex. A, p. 6.) Instead, she
notes that (i) seasonal differences in narcolepsy incidence, (ii) the rise in incidences
post 2009-2010 administration of the AS03-adjuvanted H1N1 vaccine and (iii) the
association with anti-streptococcal antibodies, all circumstantially support the theory that

25
environmental factors contribute to the development of narcolepsy in patients who are
genetically susceptible. (Ex. A, p. 6 (citing Postiglione et al., supra, at Ex. K).)

In that regard, Dr. Steinman notes three groups 22 who have “reported immune
responses to hypocretin reception 2 in narcolepsy”: (i) a group led by Dr. Steinman who
found that “in vaccine-induced narcolepsy, there are antibodies to HCRT-R2” and who
identified a region of the HCRT-R2 molecule located at the site where hypocretin binds
the receptor 23 (ii) a group in Japan which found antibodies to HCRT-R2 in narcolepsy24
and (iii) as did a group from Oxford. 25 (Ex. 14, p. 10.) Upon examination, these three
studies do not preponderantly establish HCRTR2 antibodies as the cause of
narcolepsy.

Tanaka et al. developed a study testing serum from one-hundred eighty-one
patients with narcolepsy, ten patients with other hypersomnia and ninety-one control
subjects. (Tanaka et al., supra, at 634 (Ex. 29).) As a result, they observed
autoantibodies against hypocretin in nine narcolepsy patients, HCRTR in three patients,
HCRTR1 in one patient, and HCRTR2 in five patients. (Id. at 635.) Eight of these

22
As noted above, Dr. Steinman also mentions a fourth group, Mignot’s group, who showed “some
evidence of antibodies to HCRT-R2 in narcolepsy” post Pandemrix vaccination, though he discounts
these findings due to a “major flaw” in one of the assays for HCRT-R2 that appears in their
supplementary data. (Id. (citing De la Herrán-Arita et al., supra at Ex. 25; De la Herrán-Arita et al., supra
at Ex. 26 (Retraction published on July 30, 2014)).) In the De la Herrán-Arita et al. study (2013)
(“Mignot’s group”) researchers tested for the presence of T cell reactivity toward HCRT epitopes HCRT56-
68 and HCRT87-99. (De la Herrán-Arita, supra, at Ex. 25, p. 7-9.) The results indicated that CD4 T cells
+

reactive to the presentation of HCRT56-68 and/or HCRT87-99 by DQ0602 were present in most patients with
narcolepsy. (Id. at 7.) The autoantigens primarily elicited a TH1 response, which the authors explain is
“characteristic of many autoimmune diseases.” (Id.) Yet, these results were later retracted. (De la
Herrán-Arita, supra, at Ex. 26, p. 14.) In a later article, Mignot explained that the hypocretin cell loss in
narcolepsy and the presence of the HLA DQB1*0602 is what “rekindled the hypothesis of autoimmunity,”
with hypocretin as the logical target. (Mignot, supra, at Ex. O, p. 865.) Despite this association,
“[s]uprisingly, however, autoantibodies targeting hypocretin peptides have not been found, and immune
staining of hypothalamic tissue with human narcolepsy sera has not revealed autoantibodies target
colocalized antigens on these neurons.” (Id.) Passive transfer experiments of human sera in mice have
been published, which suggested the presence of functional autoantibodies, however, Mignot explains
that these studies could not be replicated. (Id.) After the results of De la Herrán-Arita et al. study (2013),
researchers felt “a blood test for narcolepsy might be close at hand, but on finding these data were
invalid, [the authors] withdrew the paper.” (Id. at 866.) Ultimately, Mignot suggests that there is strong
circumstantial evidence supporting an autoimmune hypothesis though direct evidence is lacking. (Id.)

23 Ahmed et al., Antibodies to influenza nucleoprotein cross-react with human hypocretin receptor 2,7

(294) SCI. TRANSL. MED. (2015) (Ex. 27). Dr. Steinman notes that his group identified the region of the
HCRT-R2 molecule that was previously identified at the University of Texas Southwestern Medical
School, “precisely at the site where hypocretin binds the receptor.” (Ex. 14, p. 10) (citing Yin et al,
Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptions, 23(4) NAT.
STRUCT. MOL. BIOL. 293-9 (2016)).)

24 Tanaka et al., Detection of autoantibodies against hypocretin, hcrtr1, and hcrtr2 in narcolepsy: anti-hcrt

system antibody in narcolepsy, 29(5) SLEEP 633-638 (2006) (Ex. 29).
25 Giannocarro et al, Antibodies against HCRT-R2 are rare in narcolepsy, 40(2) SLEEP (2017) (Ex. 30.)

26
patients had anti-HCRT neurotransmission system antibodies, with one patient having
positive reactions against both HCRTR1 and 2. (Id.) However, positive reactions were
also noted against HCRTR1 in two control subjects and HCRTR2 in one control subject.
(Id. at 636.) Tanaka et al. indicated that “[anti-HCRT antibodies] might be naturally
occurring autoantibodies without pathologic function or might not cross the blood-brain
barrier to cause narcolepsy.” (Id. at 637.) The authors observed that no relationships
existed between these autoantibodies and HLA DRB1*1501/DRQB1*0602 haplotypes,
the presence of cataplexy, the presence of subjective nocturnal sleep disruption, or the
scores on the Epworth Sleepiness Scale. (Id.) Ultimately, their results do not support
the hypothesis that autoantibody-mediated dysfunction in the hypocretin system
underlies the pathophysiology of narcolepsy. (Id.)

The Ahmed et al. study suggested a possible link between the Pandemrix
vaccine (an adjuvanted, influenza pandemic vaccine) and the development of
antibodies between hypocretin receptors. (Ahmed et al., supra, at 1 (Ex. 27).) In that
study, Dr. Steinman and his colleagues hypothesized that differences in the
nucleoprotein make-up of vaccines could explain why an increased incidence of
narcolepsy was observed following one type of influenza vaccine, Pandemrix, but not a
differently manufactured influenza pandemic vaccine, Focetria. (Id.) Differences
between the protein sequences from A(H1N1) pdm09 virus and the Pandemrix and
Focetria vaccines identified an influenza nucleoprotein peptide similar to human HCRT
receptor 2. (Id. at 2.) Antibodies were detected in the blood sera of higher numbers of
Pandemrix-vaccinated participants with narcolepsy than with individuals who did not
suffer from narcolepsy. (Id.) Key to this study was the authors’ comparison of the
nucleoprotein antibody content found in individuals who received eight different
inactivated flu vaccines, in addition to three monovalent A(H1N1) pmd09 vaccines (a
group which included Pandemrix). (Id. at 4.) Of the three monovalent vaccines,
Focetria had 72.7 percent fewer nucleoproteins than Pandemrix. (Id.) This suggested
“the possibility that lower [nucleoprotein] concentrations in Focetria could have
attenuated both the immune response to nucleoprotein and the subsequent generation
of [nucleoprotein] antibodies capable of cross-reactivity with HCRT receptor 2.” (Id.)
Ahmed et al. do not propose an explanation for this difference, other than to say that the
vaccines were manufactured differently. (Id. at 1.)

In the third group cited by Dr. Steinman, Giannocarro et al. (2017), sera from fifty
narcolepsy type 1 patients and eleven narcolepsy type 2 patients, twenty-two patients
with other sleep disorders, fifteen health controls, and ninety-three disease controls
were tested for the HCRTR2 antibodies. (Giannocarro et al., supra, at 1 (Ex. 30).)
Using a live cell-based assay approach, the researchers found only three narcolepsy
patients had IgG antibodies to HCRTR2. (Id. at 4-5.) They further observed that the
titers were low in all three patients and no HCRTR2 antibodies were found in their CSF.
(Id. at 5.) The authors note the earlier study from Tanaka et al., which also found a low
proportion of patients with antibodies immunoprecipitating HCRTR2. (Id.) Taken
together, Giannocarro et al. conclude that antibodies to HCRTR2 in patients with
idiopathic narcolepsy “appear to be rare.” (Id.) The results of both studies, as well as
the low titers in the serum and the absence of CSF antibodies (which are usually

27
present in patients with typical antibody-mediated diseases) suggests that these
antibodies “may not be clinically relevant.” (Id.) However, the authors note that their
results, as well as Tanaka et al., contrast with the results from Ahmed et al. (Id.)
Giannocarro et al. suggest that their results could reflect different methodologies. (Id.)
Moreover, they acknowledge that their three positive results were atypical because one
patient presented with narcolepsy type 1 and psychosis, and two patients were
DQB1*602 negative. (Id.) Ultimately, however, they suggest that the significance of
any HCRTR2 antibodies, even in a subset of narcolepsy patients, should be interpreted
with caution.

The proposition that narcolepsy may be “an immune-mediated condition is fairly
well-established” in the Program. McCollum v. Sec'y of Health & Human Servs., No. 14-
790V, 2017 WL 5386613, at *16 (Fed. Cl. Spec. Mstr. Sept. 15, 2017), review denied,
135 Fed. Cl. 735 (2017), aff’d, 760 Fed. Appx. 1003 (2019). Other prior decisions have
observed the likelihood that narcolepsy is autoimmune. See D'Tiole v. Sec'y of Health &
Human Servs., No. 15-085V, 2016 WL 7664475 (Fed. Cl. Spec. Mstr. Nov. 28, 2016),
review denied, decision aff'd, 132 Fed. Cl. 421 (2017), aff'd, 726 F. App'x 809 (Fed. Cir.
2018); Dougherty v. Sec'y of Health & Human Servs., No. 15-1333V, 2018 WL
3989519, at *43 (Fed. Cl. Spec. Mstr. July 5, 2018), aff'd, 141 Fed. Cl. 223 (2018); E.S
v. Sec'y of Health & Human Servs., No. 17-480V, 2020 WL 9076620, at *44 (Fed. Cl.
Spec. Mstr. Nov. 13, 2020). Here, although petitioner has preponderantly established
that narcolepsy is likely an autoimmune condition, she has not preponderantly
established a causal role for HCRTR2 autoantibodies in the development of the
condition.

ii. Epidemiological Evidence

Even in the absence of an identified autoantibody, an epidemiological association
between narcolepsy and the HPV vaccination could still potentially support a causal
theory. Here again, however, epidemiological evidence showing a causal link between
the HPV vaccine and the onset of narcolepsy, or in petitioner’s case, significant
aggravation, is also absent from this case. As a general matter, it is true that petitioners
in the Vaccine Program are not required to present epidemiological evidence to
establish their causation burden under Althen. Moberly v. Sec'y of Health & Hum.
Servs., 592 F.3d 1315, 1325 (Fed. Cir. 2010). However, “[n]othing in Althen or
Capizzano requires the Special Master to ignore probative epidemiological evidence
that undermines petitioner’s theory.” D'Tiole, 726 F. App'x at 811 (citing Andreu, 569
F.3d at 1379 (“Although Althen and Capizzano make clear that a claimant need not
produce medical literature or epidemiological evidence to establish causation under the
Vaccine Act, where such evidence is submitted, the Special Master can consider it in
reaching an informed judgment as to whether a particular vaccination likely caused a
particular injury.” (emphasis added)); Grant v. Sec’y of Health & Human Servs., 956
F.2d 1144, 1148-49 (Fed. Cir. 1992) (considering negative epidemiological studies).

Partinen et al. (2012) focused on an outbreak of narcolepsy among children in
Finland in 2010. (Partinen et al., supra at 1 (Ex. 38).) The authors speculated whether

28
the cause of narcolepsy was attributable to adjuvants in the Pandemrix vaccine, or
some other environmental factors or genetic predisposition. (Id. at 7-8.) Between 2002
and 2009, 335 cases of narcolepsy (all ages) were diagnosed in Finland. (Id. at 4.) In
2010, 54 children were diagnosed with narcolepsy, a 17-fold increase. (Id. at 5.) Based
on patient records, the authors placed onset of excessive daytime sleepiness at 0-242
days after receiving the H1N1 vaccine (Pandemrix, GSK). (Id.) Yet the authors
stressed the fact that the Pandemrix flu vaccine was the only form of the vaccine
associated with an increased incidence of narcolepsy. (Id. at 7) (“there is no evidence
of an increased risk of narcolepsy with any other vaccine than the AS03 adjuvanted
Pandemrix”).

Winstone et al. (2014) sought to investigate the onset of narcolepsy among
English children who received the AS03 adjuvanted pandemic A/H1N1 2009 vaccine
(Pandemrix). (Winstone, supra, at 1 (Ex. 39).) The authors identified seventy-five
patients with narcolepsy, though only eleven received the Pandemrix vaccine before
narcolepsy onset, a “relatively small number.” (Id. at 1.) As Dr. Steinman points out,
among the eleven patients who received the Pandemrix vaccine: six patients reported
onset of narcolepsy within three months, one patient reported onset between four and
six months, and four patients reported onset between seven and fourteen months. (Id.
at 4.) However, the authors acknowledged that the small number of patients who in fact
received the Pandemrix vaccine reduces the likelihood of finding statistically significant
differences between vaccinated and unvaccinated patients. (Id. at 8.)

Szakacs et al. (2013) designed a retrospective study conducted in Sweden
where symptom onset was determined based on medical record review and telephone
interviews with parents and patients. (Szakacs et al., supra, at Ex. II).) In that study,
the median time from H1N1 vaccination to symptom onset was nine-and-a-half weeks,
with nineteen of the twenty-eight patients developing symptoms in twelve weeks or less.
(Id. at 1315.) In addition, Heier et al. (2013) conducted a study in Norway where onset
was defined by reports from physicians, based on interactions with parents or patients;
and in that study the median time from vaccination to onset was eleven weeks, with
forty-two of the fifty-eight patients experiencing clinical symptoms within six months of
vaccination. (Heier et al., supra, at Ex. JJ.) The authors, however, found no significant
difference in the incidence of narcolepsy during the second year after vaccination
compared to unvaccinated children in the same time period. (Id. at 868)

The literature cited by Drs. Deak and Steinman, discussed above, demonstrates
an increased incidence of narcolepsy after the administration of the AS03-adjuvanted
H1N1 vaccine in several European countries. Yet, there is no increased risk of
narcolepsy with either H1N1 vaccines that contained other adjuvants, such as Focetria,
or among non-adjuvanted H1N1 vaccines given in the United States. (Partinen, supra,
at Ex. E; Duffy et al., supra, at Ex. Q; Nguyen et al., supra, at Ex. R.)

Gardasil, in this case the quadrivalent vaccine, is prepared from four Human
Papillomavirus type-specific virus-like particles (VLPs) from the L1 proteins of HPV 6,
11, 16, and 18, and is entirely unrelated to the above-discussed vaccines. In contrast to

29
the above, the epidemiological study by Arnheim-Dahlstrom (2013) introduced into the
record by Special Master Millman, “show[ed] that among almost one million adolescent
girls, [the] HPV vaccine was not [r]elated causally to narcolepsy.” (ECF No. 26.) This
population-based study included all adolescent girls aged between 10 and 17 years in
Denmark and Sweden who received the quadrivalent HPV vaccine between 2006 and
2010. (Arnheim-Dahlstrom et al., supra, at 2 (ECF No. 26-1) (Court Ex. 1).) The
incidence rate for immunized subjects in this study was 2.61 incidents of narcolepsy per
100,000 person years whereas the unvaccinated rate was 1.81 per 100,000 person
years. (Id. at 8.) The authors concluded that there was no significant association
between the HPV quadrivalent vaccine and narcolepsy. (Id. at 5, 8.)

In Dr. Steinman’s interpretation of this study, he concludes that the Gardasil
vaccine is associated with a higher rate of narcolepsy compared to the unvaccinated,
“even though it may not reach so-called ‘statistical significance.’” (Ex. 14, p. 31.) In
contrast, Dr. Whitton stresses that the authors do not provide the actual p value 26 of
their findings regarding narcolepsy. (Ex. EE, p. 2; ECF No. 26-1, p. 5.) In my review, I
note that Table 2 of the study expresses a confidence interval of 95 percent for the
incidence rate for both unvaccinated and vaccinated groups showing that the lower
confidence limit for the incidence rate of narcolepsy among the vaccinated group (1.17)
is lower than the lower confidence limit for the unvaccinated group (1.34). 27 Thus, this
data does not even express confidence that the actual incidence rate is higher among
the vaccinated group at all. (ECF No. 26-1, p. 8.) Although they noted the results
should be viewed with caution, the authors likewise indicated that no safety signal was
detected by the study. (Id. at 5.) Thus, I am not persuaded by Dr. Steinman’s
subjective impression of the difference as “impressive” despite lacking statistical
significance. (Ex. 14, p. 31 (“these are large samples and the difference is impressive
in my opinion…even though it may not reach so-called ‘statistical significance.’”) See
Thompson v. Sec’y of Health & Human Servs., No. 99-436V, 2003 WL 21439672, at *18
(Spec. Mstr. Fed. Cl. May 23, 2003) (observing that “professionals in the field of
epidemiology rely upon statistical significance in order to reach valid, credible
conclusions.”)

Dr. Whitton also provides a more recent study, Hvid et al. (2018), where the
authors again studied the frequency of narcolepsy following HPV vaccination and still no
significant association between the two was identified. (Ex. EE, p. 2 (citing Hvid, et al.,
supra, at Ex. FF).) Like the earlier population-based study, researchers included all
26 P value is “the probability of obtaining by chance a result at least as extreme as that observed, even

when the null hypothesis is true and no real difference exists; when P ≤ 0.05 the sample results are
usually deemed significant at a statistically important level and the null hypothesis rejected.” P-value,
DORLAND’S MEDICAL DICTIONARY ONLINE, https://www.dorlandsonline.com/dorland/definition?id=13359
(last visited Oct. 8, 2021).

27 Confidence interval is “a type of statistical interval estimate for an unknown parameter: a range of

values believed to contain the parameter, with a predetermined degree of confidence. Its endpoints are
the confidence limits, and it has a stated probability (the confidence coefficient) of containing the
parameter.” Confidence interval, DORLAND’S MEDICAL DICTIONARY ONLINE,
https://www.dorlandsonline.com/dorland/definition?id=13359 (last visited Oct. 12, 2021).

30
women from Denmark and Sweden who received the quadrivalent HPV vaccine
between 2006-2010, only this time among women 18-44 years old. (Hvid et. al., supra,
at 155 (Ex. FF).) Among 431 reported events of narcolepsy, the authors recorded 21
reports of narcolepsy any time after vaccination, with 10 reported within 179 days post-
vaccination and 11 reported within 180 days or more. (Id. at 9.) These results were not
highlighted as “significant associations.” (Id.) Taken together, the Arnheim Dahlstrom
et al. study and the Hvid et al. study suggest no significant association between the
frequency of narcolepsy and HPV vaccination.

Dr. Deak raises a further concern that the reported timing of symptom onset is
generally prone to recall bias. (Ex. GG, p. 2.) Based on her own clinical experience,
and the insidious nature of narcolepsy onset, Dr. Deak stresses that the onset of
symptoms in a retrospective study is likely to have occurred prior to the reported time of
presentation. (Id.) Researchers in Hvid et al. acknowledge that “[f]or many of the
included outcomes, there will be a delay between onset and diagnosis.” (Hvid et al.,
supra, at 163 (Ex. FF).) For this reason, the authors included two risk periods: a 180-
day period for outcomes “with little delay between onset and diagnosis” and a period
following 180 days for outcomes “with a more insidious onset.” (Id.) Even still, despite
the large size of the cohort, the authors stress that “many of the included outcomes are
rare and null findings should be interpreted in the context of statistical power.” (Id.)

The fact that a relationship between the HPV vaccine and narcolepsy has not
been uncovered epidemiologically is not in itself fatal to petitioner’s claim. Nonetheless,
review of the above demonstrates that the epidemiological evidence that does exist
does not support petitioner’s allegations.

iii. Dr. Steinman’s Theory Regarding Molecular Mimicry

Petitioner presents the theory of molecular mimicry to “[link] the vaccination to
her subsequent, significant aggravation that led to her diagnosis of narcolepsy.” (ECF
No. 73-1.) Petitioner contends that Dr. Steinman has demonstrated that components of
the HPV vaccine present molecular mimics of hypocretin and hypocretin-2 receptor.
(Id.) Specifically, Dr. Steinman carried out BLAST searches to identify homologies
between the components of the Gardasil vaccine and various components of the
hypocretin pathway, including hypocretin itself and the HCRT-R2 receptor. (Ex. 14, p.
11.)

Dr. Steinman classifies his criteria for a “meaningful molecular mimic” as a run of
5 or more of 12 amino acids that are identical. (Id.) Dr. Whitton, however, explains that
in order to identify an amino acid sequence as a “mimic,” one cannot rely on a shared
homology alone. (Ex. C, p. 5.) Rather, mimicry is defined by the “immune response
that the sequence induces” and to be a “mimic” the amino acid sequence must “(i) []
trigger an immune response and, (ii), that response must recognize (i.e., cross-react
with) the other peptide[.]” (Id.) (emphasis in original). Unless both criteria are met, then
it is not a mimic, but merely a homology. (Id.)

31
 Indeed, “molecular mimicry is a generally accepted scientific principle, [though]
mere invocation of the scientific term does not carry a petitioner’s burden in a Program
case.” Deshler v. Sec'y of Health & Human Servs., No. 16-1070V, 2020 WL 4593162,
at *20 (Fed. Cl. Spec. Mstr. July 1, 2020) (citing Forrest v. Sec’y of Health & Human
Servs., No. 14-1046V, 2019 WL 925495, at *3 (Fed. Cl. Spec. Mstr. Jan. 18, 2019)).
This is because, as Dr. Whitton opines in this case, “the finding of sequence homology
does not necessarily mean the similarity has significance to the immune system.” Tullio
v. Sec'y of Health & Human Servs., No. 15-51V, 2019 WL 7580149, at *15 (Fed. Cl.
Spec. Mstr. Dec. 19, 2019), review granted, decision aff'd, 149 Fed. Cl. 448 (2020); see
also Caredio v. Sec'y of Health & Human Servs., No. 17-0079V, 2021 WL 4100294, at
*31 (Fed. Cl. Spec. Mstr. July 30, 2021), review granted, decision aff’d, Fed. Cl.
(2021) (“demonstration of homology alone is not enough to establish a preponderant
causation theory”) (emphasis in original) (citing Schultz v. Sec'y of Health & Human
Servs., No. 16-539V, 2020 WL 1039161, at *22 n. 24 (Fed. Cl. Spec. Mstr. Jan. 24,
2020) (“[m]ere demonstration of theoretical homology alone, based on computer-driven
searches involving databases of amino acid sequences, does not carry the day”)).

Both Drs. Steinman and Whitton rely on the study from Silvanovich et al. (2006)
in their discussions on the reliability and value of BLAST searches. It is true, as Dr.
Steinman asserts, the authors concluded that “for large proteins and an expanding
allergen database, a FASTA or BLAST bioinformatics search appears to be the
optimum method for identifying potential similarities between newly expressed proteins
and known allergens.” (Silvanovich et al., supra, at Ex. OO.) The study performed a
series of analyses to determine whether there was a scientifically justified search
window size that could identify allergen sequence characteristics, in the context of
genetically engineered crops. (Id. at 252.) Based on the results, Silvanovich et al.
concluded that searches for short amino acid sequence matches of eight amino acids or
fewer, used to identify proteins as potential cross-reactive allergens, “is a product of
chance and adds little value to allergy assessments for newly expressed proteins.” (Id.
at 258.) These results, Dr. Whitton explains, show that Dr. Steinman’s 5/12 homologies
are entirely predictable. (Ex. C, p. 9.)

The “Silvanovich standard,” as Dr. Whitton describes it, requires a window of at
least 80 amino acids in length, in which there is at least 35% amino acid identity, and
whose E-value must be lower than 3.9 x 10-7. (Silvanovich et al., supra, at Ex. OO;
Silvanovich et al., supra, at Ex. PP.) According to Dr. Whitton, none of Dr. Steinman’s
BLAST results meet these criteria. (Ex. KK, p. 6.) Even assuming arguendo that Dr.
Steinman’s BLAST results did meet these criteria, nothing in this article reveals whether
Dr. Steinman’s sequence may trigger a T cell response.

The Latorre study identified a 20 amino acid sequence in orexin that can
stimulate CD8+ T cells from a single narcolepsy patient’s spinal fluid— which Dr.
Steinman suggests confirms the BLAST searches linking the HPV vaccine and a key
portion of the orexin molecule. (Latorre, supra, at Ex. 45, p. 5; Ex. 43, p. 2-5.)
However, to challenge the validity of Dr. Steinman’s theory, Dr. Whitton compared the
short orexin sequence against the measles vaccine. (Ex. KK, pp. 14-15.) Dr. Whitton

32
identified four homologies, and then carried out the same comparison using BLAST,
and one hit was returned, containing a 5/11 homology with an E-value of 0.17. (Id. at
15.) Dr. Whitton explains that, following Dr. Steinman’s logic, these results indicate that
the measles vaccine, more likely than not, triggers narcolepsy. (Id.) Yet, “[t]he MMR
vaccine was introduced in 1963” and “no association has ever been reported between
MMR and narcolepsy.” (Id.) The mere existence of a homology to the orexin sequence,
therefore, does not “inculpate[] a vaccine.” (Id.) Accordingly, in the context of this
vaccine and this injury, Dr. Steinman’s finding of homology is not sufficient to establish
causation.

While the demonstrated homology offered by Dr. Steinman is potentially useful,
the scientific literature suggests that homologies are predictable and do not inevitably
lead to cross-reaction. There have been instances where Dr. Steinman’s use of BLAST
searches has been found to help support a finding of vaccine causation. See E.M. v.
Sec’y of Health & Human Servs., No. 14-753V, 2021 WL 3477837, at *36-39 (Fed. Cl.
Spec. Mstr. July 9, 2021) (finding persuasive Dr. Steinman’s evidence of “numerous
examples of sequences in the 2011 Fluarix vaccine and between earlier seasonal flu
vaccines, that share similar homologies with the [protein] alpha3 nicotinic AChR, which
is associated with small fiber neuropathy”); White v. Sec’y of Health & Human Servs.,
No. 15-1521, 2019 WL 7563239, at *24 (Fed. Cl. Spec. Mstr. Dec. 19, 2019) (crediting
Dr. Steinman's molecular mimicry theory and BLAST searches where there were
“sufficient homologies between the basic myelin protein and two of the strains of the
HPV L1 strains…and between MOG and all four HPV antigens in the vaccine[,]” which
could cause TM). However, Dr. Steinman’s use of BLAST search result homologies
has also separately been criticized in the absence of some evidence of cross reaction
as being mere uninvestigated hypothesis. Forrest v. Sec'y of Health & Human Servs.,
No. 14-1046V, 2019 WL 925495, at *4-5 (Fed. Cl. Jan. 28, 2019) (finding that Dr.
Steinman's theory that a flu vaccine caused TM via molecular mimicry was not
sufficiently developed to meet Petitioner's burden under Althen prong one because Dr.
Steinman had “not investigated his hypothesis[,]” other than through computerized
homologies revealing “some overlap in sequences of amino acids[.]”) Even where Dr.
Steinman has shown in a separate context that a 5 out of 12 homology can be
experimentally shown to cause disease, homology alone does not in any given instance
show that a causal relationship exists between vaccine and injury. 28

28 Dr. Steinman relies upon animal studies in which researchers studying multiple sclerosis sought to

induce paralysis in mice using mimics of myelin basic protein. Dr. Steinman derives his criteria for a
“meaningful molecular mimic” from studies where scientists induced experimental allergic
encephalomyelitis (“EAE”) in mice using a viral peptide with homology with myelin basic protein. (See Ex.
14 at 11.) Similarly, Dr. Steinman cites Ufret-Vicenty et al., wherein researchers “passively transferred T
cells that cross-reacted with myelin basic protein and HPV, and saw that the experimental animals
became paralyzed[.].” (Ex. 14 at 26 (discussing Ex. 35)). Dr. Steinman fails to explain why these animal
studies involving a different protein and a different disease are relevant to petitioner’s case. See D.G. v.
Sec'y of Health & Human Servs., No. 11-577V, 2019 WL 2511769, at *77 (Fed. Cl. Spec. Mstr. May 24,
2019) (“[I]t [is] irrelevant that Dr. Steinman can make mice ill with inflammation of their brains and spinal
cords with a mere homology of five amino acids,” as “[p]etitioner is not a mouse” and “never had
inflammation of her brain or spinal cord.”)

33
 In fact, as Dr. Steinman points out, the significance of the homology is informed
by other areas of inquiry. (See Ex. 14, p. 28-29 (“[o]ther genetic and environmental
factors are necessary before these self-reactive immune responses to myelin for
example, or to HCRT-R2, may trigger inflammation in the brain.”).) In this case,
however, the other available areas of inquiry do not support a causal relationship for all
the reasons discussed in the two preceding sections.

Overall, I am more persuaded by Dr. Whitton’s opinion (discussed in much
greater detail above) that Dr. Steinman is not in this case generating reliable evidence
of molecular mimicry via his BLAST searches. Thus, I find that petitioner has not
provided a medical theory causally connecting the HPV vaccine to her worsening
narcolepsy, and petitioner is therefore unable to carry her burden under prong 4 of the
Loving test. In the Vaccine Program, it is well understood that petitioners are not
obligated to prove the precise mechanism as a component of their causation theory.
Kottenstette v. Sec'y of Health & Human Servs., No. 2020-2282, 2021 WL 2434329, at
*7 (Fed. Cir. June 15, 2021); Knudsen, 35 F.3d at 548-59. Yet, when a mechanism is
presented as the basis for petitioner’s theory, it must be based on sound and reliable
scientific explanation. Boatmon, 941 F.3d at 1359-60.

b. Significant Aggravation (Loving prongs one through three)

Assuming arguendo that petitioner did prove a medical theory demonstrating that
her HPV vaccination could have caused or aggravated her narcolepsy, the remainder of
the Loving test queries whether petitioner would be able to show that it did do so in this
particular case. The threshold question in that remaining analysis is whether
petitioner’s condition was, in fact, significantly aggravated. To demonstrate significant
aggravation, the Vaccine Act requires a “change for the worse in a preexisting
condition,” and “markedly greater disability, pain, or illness accompanied by substantial
deterioration of health.” 42 U.S.C. § 300aa-33(4). Under the Loving test, petitioner
demonstrates this by showing (1) her condition before the vaccination, (2) her current
condition, and (3) that her current condition constitutes a significant aggravation of her
prior condition.

In this case, there is no dispute that petitioner had at least some initial symptoms
of narcolepsy prior to vaccination and that she developed additional symptoms after the
vaccination. (ECF No. 73 (citing Ex. 3, pp. 43, 48); ECF No. 75 (citing Ex. 3, p. 43.))
What is contested, however, is Dr. Steinman’s assertion that the Gardasil vaccine
“changed the trajectory” of her condition. (Ex. 14, pp. 6, 31; ECF No. 75, p. 40.) There
are two cases, Locane and Sharpe, that illustrate the Circuit’s significant aggravation
analysis with regard to the evolution of petitioner’s clinical course. Locane v. Sec’y of
Health & Human Servs., 685 F.3d 1375 (Fed. Cir. 2012); Sharpe v. Sec’y of Health &
Human Servs., 964 F.3d 1072 (Fed. Cir. 2020).

In Locane, petitioner alleged her Crohn’s disease, an inflammatory bowel
disease, was significantly aggravated by the hep B vaccine. Locane, 685 F.3d at 1377-
78. The special master determined that petitioner failed to show “by a preponderance

34
of the evidence that she was entitled to compensation under the significant aggravation
theory because the course of her disease was not affected by the vaccination.” Id. at
1378. The Federal Circuit found that the special master’s finding—that petitioner’s
clinical course was not inconsistent with the disease generally and not affected by the
vaccinations—was considered from “the relevant evidence of record, [drawn from]
plausible inferences and articulated a rational basis for the decision,” therefore, the
decision was not arbitrary or capricious. Id. at 1381-82. The Court continued, stating
that petitioner was “given ample opportunity to develop her significant aggravation claim
but ‘failed to present persuasive evidence that separates [her] problems from an
expected course of Crohn's disease.’” Id. at 1382.

In Sharpe, petitioner alleged L.M. had a pre-existing “seizure disorder” and the
administration of the several childhood vaccines at her six-month wellness check-up
significantly aggravated L.M.’s pre-existing condition. Sharpe, 964 F.3d at 1076-77.
The special master denied petitioner’s significant aggravation claim because L.M.’s
genetic mutation, and not the vaccination, was the sole, substantial cause of L.M.’s
seizure disorder. Id. at 1080. The Circuit found the special master’s analysis “required
[p]etitioner to prove the expected outcome for a child with a DYNC1H1 gene mutation
and to show that L.M.’s current, post-vaccination condition was worse than that
expected outcome.” Id. at 1081. The Circuit stated, “a court should consider all
evidence in the record, including evidence of other possible sources of injury. There is,
however, a fine line between a court properly considering evidence in the record . . .
and improperly placing the burden on the petitioner to prove that her significantly
aggravated condition was not caused by her gene mutation.” Id. at 1082. The Court
distinguished the special master’s decision from Locane stating, in Locane “the special
master did not require the petitioner to prove that her significantly aggravated condition
was not caused by her preexisting condition. Instead, the special master found that the
petitioner’s condition ‘was not affected by the vaccination.’” Id.

In this case, petitioner presented to the emergency department on May 11, 2013,
with symptoms of sleep disruption and daytime sleepiness with prolonged napping 4-6
weeks prior to her hospitalization. (Ex. 3, p. 42; Ex. 4, p. 52.) Several other physicians
also noted sleep disruption and daytime sleepiness with prolonged napping prior to her
hospitalization. (Ex. 3, p.43, Ex. 4, p. 52 (Dr. Neiderman); Ex. 3, p.85 (Dr. Martinez);
Ex. 3, pp. 5-6, Ex. 4, p. 9, Ex. 11, p. 31 (Dr. Dubrovsky); Ex. 3, p. 66 (Dr. Brown); Ex. 3,
p. 48 (Dr. Maragh), Ex. 3, p. 54 (Dr. Chiang); Ex. 3, 69 (Dr. Gutierrez).) In one note,
petitioner described “waking up 1-2 [times] a night 4 weeks ago.” (Ex. 3, p. 5.) This
would place onset of petitioner’s symptoms in approximately April 2013, prior to the
vaccination at issue. Petitioner reported additional symptoms between 2-4 weeks prior
to hospitalization, including: legs buckling (Ex. 3, p. 65, Ex. 3, p. 85), falls (Ex. 3, p. 65,
Ex. 3, p. 69), slurred speech (Ex. 3, pp. 5-6), and gait difficulties (Ex. 3, p. 68, Ex. 3, p.
85).

Dr. Deak explains that the full narcoleptic tetrad of symptoms–excessive daytime
sleepiness, cataplexy, hypnagogic/hypnopompic hallucinations and sleep paralysis–is
rarely present at initial presentation. (Ex. A, p. 5.) The order in which symptoms appear

35
can also vary. (Id. (citing Dauvilliers et al., supra, at Ex. H).) Due to the “insidious
onset” of narcolepsy, as well as accompanying behavioral, metabolic, and mood
symptoms, narcolepsy is often misdiagnosed. (Ex. A, p. 5.) In fact, petitioner’s case
“followed a typical time course for pediatric narcolepsy,” with excessive daytime
sleepiness and nocturnal sleep disruption as her initial symptoms. (Id. at 6.) Dr. Deak
explains that “[i]t is not surprising that [petitioner] developed cataplectic active
phenomenon, in addition to negative phenomenon already present, as her symptoms
progressed.” (Ex. GG, p. 1.) I am persuaded by Dr. Deak’s assessment of petitioner’s
progression of narcolepsy: petitioner exhibited “symptoms represent[ing] a clear change
from [petitioner’s] baseline” and a “significant alteration in functioning” well before her
vaccination. (Ex. A, p. 4)

Dr. Steinman suggests that, although petitioner reported symptoms prior to the
May 1, 2013 immunization, “there was clear worsening” approximately 10 days after the
May 1, 2013, Gardasil shot. (Ex. 14, p. 31.) He quotes the “history of present illness” in
Dr. Lazar’s discharge summaries from May 16, 2013 which details “twitching” episodes
in petitioner’s left upper extremity and left leg, as well as episodes of light headedness
and falling. 29 (Id. (See Ex. 11, p. 2.) Dr. Steinman stresses that “[t]his type of activity
was NOT present prior to the May 1, 2013, immunization, based on the
contemporaneous record.” (Id.) (emphasis in original). Petitioner also asserts that her
case of narcolepsy is an “outlier,” one which presented with a “fast evolution and
diagnosis.” (ECF No. 73, p. 30.) Though petitioner notes that she suffered many of the
hallmark symptoms of narcolepsy, she contends that she “did so in a seemingly
abbreviated time frame compared to many children.” (Id.) Citing to the Aran et al.
study, petitioner suggests that petitioner’s case falls within a time frame of three months
between onset of sleepiness in children and development of cataplexy. (Id. at 29.)

Yet the authors of that study report that “[c]ataplexy occurred within 3 months of
onset in 85% of cases,” and within 2 months of onset in 82% of cases. (Aran et al.,
supra, at Ex. I.) These time frames fit squarely with the progression of petitioner’s
alleged symptoms. Additionally, the medical records suggest that petitioner was
already experiencing symptoms suggestive of cataplexy prior to her vaccination. In fact,
several providers documented symptoms of cataplexy, including legs buckling (Ex 3. pp.
65, 85, 90), falls (Ex. 3, pp. 65, 85), slurred speech (Ex. 3, pp. 5-6, 51), 30 and gait
difficulties (Ex. 3, p. 68) during the 2-4 weeks prior to hospitalization. The providers

29 (See Ex. 3, p. 43 (On May 11, 2013 “[m]other reports slurred speech and hands twitching and shaking
started 3 days ago, knees twitching (while standing) started 2.5 weeks ago and the sleeplessness started
6 weeks ago.); (Ex. 3, p. 48 (On May 11, 2013 “[o]ver the past three days [petitioner] report[ed]
“twitching” of her left upper extremity and left leg”); (Ex. 3, p. 71 (same)).

30 Dr. Neidenberg’s narrative from May 11, 2013 states that “slurred speech and hands twitching and

shaking started 3 days ago.” (Ex. 3, p. 43.) While Dr. Deray’s report from June 27, 2013 suggests that
petitioner’s slurred speech began approximately four days after the Gardasil shot. (Ex. 9, p. 6.)
Petitioner’s discharge summary, which petitioner’s mother claims is the most accurate summary of
petitioner’s onset of symptoms, simply notes that “Mother reports that at time patient’s speech was noted
to be ‘slurred,’” without any indication of onset. (Ex. 11, p. 2.)

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documented the presence of the above symptoms preceding vaccination based on real-
time interviews with petitioner and her mother.

In light of the above, I do not find preponderant evidence on this record that
petitioner’s vaccination significantly aggravated her condition. I have not required
petitioner to prove that her post-vaccination condition was worse than the expected
outcome. Instead, I find that the evidence taken as a whole shows that her course was
not inconsistent with pediatric narcolepsy generally and that her condition was not
affected by the vaccination. This finding is consistent with Locane. It is also further
reinforced by the discussion of the treating physician opinions below.

c. Logical sequence of cause and effect showing the vaccination was
the reason for the injury (Althen prong two/Loving prong five)

The second Althen prong/fifth Loving prong requires proof of a logical sequence
of cause and effect showing that the vaccine was the reason for the injury, usually
supported by facts derived from a petitioner's medical records. Althen, 418 F.3d at
1278; Andreu, 569 F.3d at 1375–77; Capizzano v. Sec’y of Health & Human Servs., 440
F.3d 1317, 1326 (Fed. Cir. 2006); Grant, 956 F.2d at 1148. However, medical records
and/or statements of a treating physician do not per se bind the special master to adopt
the conclusions of such an individual, even if they must be considered and carefully
evaluated. See 42 U.S.C. §300aa-13(b)(1) (providing that “[a]ny such diagnosis,
conclusion, judgment, test result, report, or summary shall not be binding on the special
master or court”); Snyder v. Sec'y of Health & Human Servs., 88 Fed. Cl. 706, 746 n.67
(2009) (“there is nothing ... that mandates that the testimony of a treating physician is
sacrosanct—that it must be accepted in its entirety and cannot be rebutted”). Dr.
Steinman’s assessment of a vaccine-caused “change in trajectory” is addressed above.
Here, I additionally note that there is not preponderant evidence that petitioner’s treating
physicians concluded that her HPV vaccination caused a significant aggravation of her
preexisting narcolepsy.

The medical record closest to supporting petitioner’s contention is Dr.
Dubrovsky’s note that petitioner “presented with excessive daytime sleepiness,
cataplexy, and episodes of sleep paralysis since mid April, exacerbated after Gardasil
shot at the end of April.” (Ex. 11, p. 31.) At this visit, Dr. Dubrovsky also
recommended reporting petitioner’s condition “to the registry” (presumably referring to
the Vaccine Adverse Event Reporting System (VAERS). (Id.) Importantly, however,
she made a point of specifically noting in the same assessment that “I am not certain[] if
the symptoms are associated with the vaccination.” (Id.) Dr. Dubrovsky previously
wrote that she “wonder[ed] if the vaccination ha[d] anything to do with the escalating of
the symptoms.” (Ex. 3, p. 6.) Considering Dr. Dubrovsky’s records as a whole, her
statements of mere suspicion fall short of an opinion supporting a vaccine-related
significant aggravation of petitioner’s condition. See Stapleford v. Sec’y of Health &
Human Servs., No. 03-234V, 2009 WL 1456441, at *17 n.24 (Fed. Cl. Spec. Mstr. May
1, 2009) (referencing medical record “is quite different from an indication that such
physician has reached a conclusion concerning a causal relationship”) (emphasis in

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original), aff’d, 89 Fed. Cl. 456 (Fed. Cl. 2009). Moreover, “[a] treating physician’s
recognition of a temporal relationship does not advance the analysis of causation.”
Isaac v. Sec’y of Health & Human Servs., No. 08-601V, 2012 WL 3609993, at *26 (Fed.
Cl. Spec. Mstr. July 30, 2012); see also Devonshire v. Sec’y of Health & Human Servs.,
No. 99-031V, 2006 WL 2970418, at *19 (Fed. Cl. Spec. Mstr. Sept. 28, 2006) (medical
expert’s “post hoc ergo prompter hoc reasoning…has been consistently rejected by the
Court and is ‘regarded as neither good logic nor good law’”) (quoting Fricano v. U.S., 22
Cl. Ct. 796, 800 (1991) (emphasis in original)).

The records from petitioner’s other treating physicians regarding causation were
no less equivocal. Pediatric neurologist Dr. Martinez questioned whether petitioner’s
symptoms “could possibly be a side effect of Gardasil,” but ultimately concluded that the
“etiology of [petitioner’s] symptoms [is] unknown” and speculated that her symptoms
could be due to green coffee extract that petitioner was taking. (Ex. 3, pp, 90, 102.) Dr.
Stuart Brown also questioned whether petitioner’s Gardasil vaccination “triggered []
narcolepsy on an autoimmune basis,” noting that “[t]his has been reported occasionally
with other immunizations,” but with respect to Gardasil, “the statistics for this are
questionable as to a cause and effect relationship.” (Id. at 66.) Pediatric infectious
disease specialist Dr. Robert Reid also examined petitioner and concluded that her
condition was “not likely a reaction to the vaccine since the symptoms of insomnia
started way before the vaccine was given.” (Id. at 53.) Dr. Gutierrez, a second pediatric
infectious disease specialist, observed that petitioner “had received the Gardasil
[vaccine] after the symptoms had started” and did “not believe there has been any
association.” (Id. at 70.)

On the whole, I find that petitioner’s treating physicians considered, though did
not conclude, that petitioner’s HPV vaccine significantly aggravated her preexisting
narcolepsy. See Cedillo v. Sec’y of Health & Human Servs., 617 F.3d 1328, 1348 (Fed.
Cir. 2010) (special master did not err in affording little weight to the opinions of
petitioner’s treating physicians where “none of the treating physicians concluded that
the MMR vaccine caused [petitioner’s] autism”); Moberly, 592 F.3d at 1324-25 (finding
no treating physician evidence to support the claim of causation where the “medical
records regarding the temporal proximity of the [vaccination] to the seizures were all
speculative.”)

Other records suggest that petitioner’s treating physicians considered Gardasil
as a possible cause of petitioner’s narcolepsy in large part due to her mother’s
prompting. (See Ex. 3, p. 100 (“[m]other has concerns that the [petitioner] had a
Gardasil [sic] immunization at [sic] this may have contributed to the [petitioner’s]
symptoms”); Ex. 48, p. 29 (petitioner’s “mom related [daughter’s illness] to the gardasyl
[sic] shot”); Ex. 3, pp. 62-63 (petitioner’s “mother believes that some of [petitioner’s]
symptoms have occurred shortly after her Gardasil vaccination.”)) That petitioner’s
treating physicians noted her mother’s concerns in their records, however, provides little
support for the proposition that they themselves believed Gardasil to be a cause for
petitioner’s condition. E.g., Moriarty by Moriarty v. Sec'y of Health & Human Servs., No.
03-2876V, 2014 WL 4387582, at *15 (Fed. Cl. Spec. Mstr. Aug. 15, 2014) (petitioner’s

38
parent’s “views about causation are not persuasive because she is not a medical
doctor’”), review denied, decision aff'd, 120 Fed. Cl. 102 (2015), vacated and remanded
on other grounds, 844 F.3d 1322 (Fed. Cir. 2016); accord 42 U.S.C. § 300aa–13 (a
special master may not find in favor of the petitioner “based on the claims of a petitioner
alone, unsubstantiated by medical records or medical opinion”); James-Cornelius v.
Sec’y of Health & Human Servs., 984 F.3d 1374, 1380 (Fed. Cir. 2021) (“lay opinions as
to causation or medical diagnosis may be properly characterized as mere ‘subjective
belief’ when the witness is not competent to testify on those subjects[.]”)

Lastly, petitioner also contends that “[t]here is no evidence of another factor that
may have exacerbated her narcolepsy.” (ECF No. 73, p. 27.) In this Program,
however, absence of another cause is not persuasive evidence in support of petitioner’s
burden to show causation. See D.G., 2019 WL 2511769, at *183 (“[T]he Federal Circuit
in Grant state[]d [that] petitioner’s burden is to prove vaccine causation with affirmative
evidence. Saying since there is no other cause, it has to the vaccine is not affirmative
proof.”) (citing Grant, 956 F.2d at 1149).

d. Proximate temporal relationship between vaccination and injury
(Althen prong three/Loving prong six)

The third Althen prong/sixth Loving prong requires establishing a “proximate
temporal relationship” between the vaccination and the injury alleged. Althen, 418 F.3d
at 1281. That term has been equated to the phrase “medically-acceptable temporal
relationship.” Id. A petitioner must offer “preponderant proof that the onset of
symptoms occurred within a timeframe which, given the medical understanding of the
disorder's etiology, it is medically acceptable to infer causation.” de Bazan v. Sec'y of
Health & Human Servs., 539 F.3d 1347, 1352 (Fed. Cir. 2008). The explanation for
what is a medically acceptable timeframe must also coincide with the theory of how the
relevant vaccine can cause an injury. Id.; Shapiro v. Sec'y of Health & Human Servs.,
101 Fed. Cl. 532, 542 (2011), recons. den'd after remand, 105 Fed. Cl. 353 (2012), aff'd
mem., 503 Fed. Appx. 952 (Fed. Cir. 2013); Koehn v. Sec'y of Health & Human Servs.,
No. 11–355V, 2013 WL 3214877, at *26 (Fed. Cl. Spec. Mstr. May 30, 2013), mot. for
review den'd (Fed. Cl. Dec. 3, 2013), aff'd, 773 F.3d 1239 (Fed. Cir. 2014).

Petitioner received her second HPV vaccination on May 1, 2013. (Ex. 4, pp. 70-
71.) Petitioner was subsequently hospitalized ten days later, on May 11, 2013. (Ex. 3,
p. 43.) Thus, petitioner contends that her medical records show “an increase of
narcolepsy symptoms in the span of four to ten days after receipt of the May 1, 2013
vaccination.” (ECF No. 73, p. 31.) However, petitioner’s Althen prong three / Loving
prong six argument lacks a reliable medical or scientific explanation for how her HPV
vaccine significantly aggravated her narcolepsy. Dr. Steinman relies solely on literature
evaluating the onset of narcolepsy following the administration of another vaccine, the
Pandemrix H1N1 influenza vaccine, to establish a temporal relationship between the
HPV vaccination and worsening of petitioner’s narcolepsy. (Ex. 14, pp. 32-33
(discussing Partinen et al., supra, at Ex. 38; Winstone et al., supra, at Ex. 39).)

39
 Although the timing in this case is consistent with what is generally thought to be
an appropriate timeframe for the adaptive immune response underlying the molecular
mimicry theory in other contexts, the specific data from these Pandemrix studies cannot
be extrapolated to the HPV vaccine where an increased risk of narcolepsy has not been
shown. (See Arnheim-Dahlstrom et al., supra, at ECF No. 26; Hvid et. al., supra, at Ex.
FF.) This is especially true “in a case like the present, where a vaccine’s formulation
bears heavily on [p]etitioner’s claim[.]” D’Tiole, 2016 WL 7664475, at *22 (citations
omitted). Where “[p]etitioner wants to leverage findings about a different vaccine
formulation [and] epidemiologic evidence relevant to the version of the vaccine in
dispute,” here the HPV vaccine, such findings “ought to be weighed against [p]eitioner’s
proof in evaluating whether [s]he has carried h[er] overall burden.” Id.

VII. Conclusion

Petitioner has my sympathy for the pain and suffering she endured during her
hospitalization and the symptoms she suffers from presently. However, for all the
reasons discussed above, after weighing the evidence of record within the context of his
program, I cannot find by preponderant evidence that the HPV vaccine significantly
aggravated petitioner’s narcolepsy. Accordingly, this claim is DISMISSED. 31

IT IS SO ORDERED.

s/Daniel T. Horner
Daniel T. Horner
Special Master

31In the absence of a timely-filed motion for review of this Decision, the Clerk of the Court shall enter
judgment accordingly.

40